Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging.

Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH2I2 and CH2BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH2I2, the structural evolution of the neutral molecule was simultaneously characterized along the C-I and I-C-I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Exacerbations of Severe Asthma While on Anti-IL-5 Biologics.

Anti-interleukin 5 (IL-5) and anti-IL-5 receptor α monoclonal antibodies markedly decrease airway and peripheral blood eosinophil numbers and are thus highly effective in reducing asthma exacerbations. Nonetheless, these biologics do not completely resolve exacerbations. There is very little information on the cellular nature of exacerbations during treatment with biologics. Using illustrative clinical case scenarios, we highlight the importance of carefully characterizing asthmatics at the time of exacerbation and recognizing neutrophilic causes of exacerbations to ensure optimal management. While an eosinophilic exacerbation may improve with more corticosteroids or by switching to another anti-IL-5 monoclonal antibody, a noneosinophilic exacerbation will likely not. An infective exacerbation needs to be recognized, and the pathogen must be identified and treated with the appropriate antimicrobial agent.

Cleaning of used rotary nickel-titanium files in an ultrasonic bath by locally intensified acoustic cavitation.

AIM: To compare the pre-sterilization cleaning of rotary Ni-Ti files of different sizes previously used a. ex vivo and b. clinically by a washer-disinfector, a regular ultrasonic bath, and the same ultrasonic bath in combination with a recently developed cavitation intensifying method. METHODOLOGY: Two sets of two hundred rotary Ni-Ti files, one previously used ex vivo and another one used clinically, were collected from the undergraduate and postgraduate clinics of the Academic Centre for Dentistry Amsterdam (ACTA). The instruments were immersed in an enzymatic solution and subsequently cleaned either by a washer-disinfector, a regular ultrasonic bath combined with a glass beaker, the same bath combined with a beaker lined with two cavitation intensifying sheets or with two standard plastic sheets. The positive control consisted of used files that did not undergo any cleaning and the negative control included new unused files. The instruments were then stained to reveal remaining protein material and scored under a stereoscopic microscope. The results were analysed by nonparametric statistical tests (α = 0.05). RESULTS: No significant difference was found between the combination of the ultrasonic bath and the regular glass beaker and the same ultrasonic bath with the beaker lined with the cavitation intensifying sheets. The washer-disinfector left significantly more debris compared to the latter group when clinically used files were evaluated (P ≤ 0.001). The effect of instrument size on cleaning was not consistent. CONCLUSION: None of the tested methods was able to remove all residual protein material from the files; however, it could be noted that this study did not follow the reprocessing protocol provided by the manufacturer.

Match activity and physiological load in wheelchair tennis players: a pilot study.

STUDY DESIGN: There is a lack of information about the physiological and psychological parameters in competition that shows a comprehensive profile of the demands of the game situation. OBJECTIVE: The aim of the present study was to examine the activity patterns and physiological-perceptual responses (heart rate (HR), blood lactate concentrations (LA) and the rate of perceived exertion (RPE), respectively, during singles wheelchair tennis (WT) matches. METHODS: A total of four WT players played three matches each. HR, LA and RPE were measured during each match. An activity pattern analysis was performed during all matches. Furthermore, LA and RPE were compared between service and return games. RESULTS: The results show a mean (s.d.) total match time of 69.04 (2.3) minutes, an effective playing time of 17.65% (0.03%), a work:rest (W:R) time ratio of 1:4.6 (0.48) and a rally length of 7.04 (4.44) seconds. Most of the points end in three or fewer shots. The mean (s.d.) physiological load during the matches were as follows: HR 124.25 (24.7) beats per minute, %HRmax 66.31% (4.5%), LA 1.41 (0.43) mmol l(-)(1) and RPE 12.45 (1.91). No significant differences were found in LA and RPE between service and return games (P>0.05). CONCLUSIONS: In this descriptive study, match activity and physiological load in WT are described. Match activities are similar to conventional tennis, although the physiological load is lower. Service and return situations show similar physiological and perceptual responses. These results might be used to develop specific interval training protocols for a male WT player.

Psychophysiological stress responses during training and competition in young female competitive tennis players.

This study sought to compare the psychophysiological stress responses during an actual competitive game and a training session in a group of high-level young female tennis players. 12 players were monitored during one match and a training day (i.e., simulated match play). Measurements included salivary cortisol (SC), the revised Competitive Sport Anxiety Inventory, heart rate (HR), and rate of perceived exertion (RPE). Match day elicited higher SC levels for losers at all points in time when compared to winners. All players showed significantly lower SC levels during training when compared to the match at all points in time except during the evening for winners. Winners of match and training situations had significantly higher self-confidence and lower cognitive anxiety and somatic anxiety scores than losers. Heart rate and RPE were significantly higher for losers only during the match (158.9±8.3 vs. 168±6.7 bpm; 12.9±1.2 vs. 15±0.8, for losers and winners, respectively). There were moderate to strong correlations between SC, self-confidence and anxiety scores, and match workload (i.e., HR and RPE) only during the match day. These results indicate that the interplay between psychophysiological responses, match workload and outcome was evident only under real competitive situations.

Time resolved emission at 1.3 µm of a single InAs quantum dot by using a tunable fibre Bragg grating.

Photoluminescence and time resolved photoluminescence from single metamorphic InAs/GaAs quantum dots (QDs) emitting at 1.3 µm have been measured by means of a novel fibre-based characterization set-up. We demonstrate that the use of a wavelength tunable fibre Bragg grating filter increases the light collection efficiency by more than one order of magnitude as compared to a conventional grating monochromator. We identified single charged exciton and neutral biexciton transitions in the framework of a random population model. The QD recombination dynamics under pulsed excitation can be understood under the weak quantum confinement potential limit and the interaction between carriers at the wetting layer and QD states.

Enhanced optical conductivity and many-body effects in strongly-driven photo-excited semi-metallic graphite.

The excitation of quasi-particles near the extrema of the electronic band structure is a gateway to electronic phase transitions in condensed matter. In a many-body system, quasi-particle dynamics are strongly influenced by the electronic single-particle structure and have been extensively studied in the weak optical excitation regime. Yet, under strong optical excitation, where light fields coherently drive carriers, the dynamics of many-body interactions that can lead to new quantum phases remain largely unresolved. Here, we induce such a highly non-equilibrium many-body state through strong optical excitation of charge carriers near the van Hove singularity in graphite. We investigate the system's evolution into a strongly-driven photo-excited state with attosecond soft X-ray core-level spectroscopy. We find an enhancement of the optical conductivity of nearly ten times the quantum conductivity and pinpoint it to carrier excitations in flat bands. This interaction regime is robust against carrier-carrier interaction with coherent optical phonons acting as an attractive force reminiscent of superconductivity. The strongly-driven non-equilibrium state is markedly different from the single-particle structure and macroscopic conductivity and is a consequence of the non-adiabatic many-body state.

Differentiating multi-MeV, multi-ion spectra with CR-39 solid-state nuclear track detectors.

The development of high intensity petawatt lasers has created new possibilities for ion acceleration and nuclear fusion using solid targets. In such laser-matter interaction, multiple ion species are accelerated with broad spectra up to hundreds of MeV. To measure ion yields and for species identification, CR-39 solid-state nuclear track detectors are frequently used. However, these detectors are limited in their applicability for multi-ion spectra differentiation as standard image recognition algorithms can lead to a misinterpretation of data, there is no unique relation between track diameter and particle energy, and there are overlapping pit diameter relationships for multiple particle species. In this report, we address these issues by first developing an algorithm to overcome user bias during image processing. Second, we use calibration of the detector response for protons, carbon and helium ions (alpha particles) from 0.1 to above 10 MeV and measurements of statistical energy loss fluctuations in a forward-fitting procedure utilizing multiple, differently filtered CR-39, altogether enabling high-sensitivity, multi-species particle spectroscopy. To validate this capability, we show that inferred CR-39 spectra match Thomson parabola ion spectrometer data from the same experiment. Filtered CR-39 spectrometers were used to detect, within a background of ~ 2 × 1011 sr-1 J-1 protons and carbons, (1.3 ± 0.7) × 108 sr-1 J-1 alpha particles from laser-driven proton-boron fusion reactions.

Non intubated video-assisted thoracoscopic lung resections (NI-VATS) in COVID times.

The emergence of epidemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan, China causing Coronavirus Disease 2019 (COVID-19) and its rapid expansion around the world, leading to a global pandemic of dimensions not observed at least since the "Spanish influenza" pandemic in 1917-18, has had great consequences at all levels, including social, health and economic spheres. This pandemic situation forces us, as health care workers, to redefine our medical and surgical actions to adapt them to this new reality. It is important, when the rules of the game change, to rethink and to reevaluate if the balance between risk and benefit have moved to a different point of equilibrium, and if our indications of certain surgical interventions need to be redefined. In this article we try to answer the doubts that arise about the suitability of the NI-VATS technique and assess whether its use in these new pandemic circumstances might add advantages, especially in relation to minimize the risks of virus contagion between patients and all healthcare personnel during the surgical procedure, as well as the known advantages described in many articles the last ten years.

Incidental finding of cornea verticillata or lamellar inclusions in kidney biopsy: measurement of lyso-Gb3 in plasma defines between Fabry disease and drug-induced phospholipidosis.

INTRODUCTION: Therapy with cationic amphiphilic drugs (Amiodarone or hydroxychloroquine) may result in biochemically and ultrastructurally similar lipid inclusions in many cells also affected by Fabry disease (FD). In addition, it often results in similar clinical manifestations such as cornea verticillata. This may lead to a FD misdiagnosis, especially when a complete medical history is not available to the ophthalmologist confronted with cornea verticillata or to the pathologist examining a kidney biopsy. When enzymatic/genetic test or pathological studies are not conclusive, a specific biomarker may help clarify this dilemma. The plasma globotriaosylsphingosine (lyso-Gb3) assay has high sensitivity and specificity and is elevated above normal levels in FD. MATERIALS AND METHODS: We measured plasma lyso-Gb3 levels in male patients receiving Amiodarone or hydroxychloroquine and compared it with male patients with classic and late onset variant of FD. RESULTS: In all Fabry patients (classic and late onset variant) α-GalA activity was deficient in dried blood spot and plasma lyso-Gb3 was above normal levels. Patients on treatment with Amiodarone or hydroxychloroquine had normal values for α-GalA activity and lyso-Gb3 in plasma. CONCLUSIONS: Even when Amiodarone or hydroxychloroquine may decrease α-GalA activity in vitro or in cell culture, our results showed that in all patients lyso-Gb3 plasma levels remain normal with no evidence of reduction in α-GalA activity, confirming the specificity of this biomarker for the diagnosis of FD.

A randomized, controlled, open-label trial evaluating the efficacy and safety of chloroquine in the treatment of giardiasis in children.

BACKGROUND: Giardia duodenalis is among the commonest protozoan parasites in the intestinal tract of humans and may cause significant morbidity worldwide. Although there are several antigiardial agents, treatment failures have been commonly reported. OBJECTIVE: To compare the efficacy and safety of chloroquine (CQ) versus metronidazole (MTZ) in the treatment of children with confirmed G duodenalis mono-infection. METHODS: A randomized, controlled, open-label trial was carried out at the Cuban Institute of Gastroenterology. One hundred and twenty-two children were randomly assigned to receive either CQ (10 mg/Kg bodyweight twice a day for five days) or MTZ [15 mg/Kg bodyweight divided in three daily does for five days]. All children were asked to provide three faecal samples on days 3, 5 and 7 after treatment completion. Children were considered to be cured, if no Giardia trophozoites or cysts were found in any of the three post-treatment faecal specimens evaluated by direct wet mounts and/or after Ritchie concentration techniques. RESULTS: The frequency of cure was a little higher for CQ than for MTZ but the difference was not statistically significant. Headache was more common in patients treated with CQ as was bitter taste. Yellowish colouration of the urine was more frequent in the MTZ treated group. CONCLUSION: Chloroquine, for five days, is as efficacious as the recommended treatment with MTZ in children infected with G duodenalis.

Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) drives migration and progression of T-cell acute lymphoblastic leukemia in vitro and in vivo.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer. There are no immunotherapies and few molecularly targeted therapeutics available for treatment of this malignancy. The identification and characterization of genes and pathways that drive T-ALL progression are critical for the development of new therapies for T-ALL. Here, we determined that the protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) plays a critical role in T-ALL initiation and progression by promoting leukemia cell migration. PRL-3 is highly expressed in patient T-ALL samples at both the mRNA and protein levels compared to normal lymphocytes. Knock-down of PRL-3 expression using short-hairpin RNA (shRNA) in human T-ALL cell lines significantly impeded T-ALL cell migration capacity in vitro and reduced their ability to engraft and proliferate in vivo in xenograft mouse models. Additionally, PRL-3 overexpression in a Myc-induced zebrafish T-ALL model significantly accelerated disease onset and shortened the time needed for cells to enter blood circulation. Reverse-phase protein array (RPPA) and gene set enrichment analysis (GSEA) revealed that the SRC signaling pathway is affected by PRL-3. Immunoblot analyses validated that manipulation of PRL-3 expression in T-ALL cells affected the SRC signaling pathway, which is directly involved in cell migration, although Src was not a direct substrate of PRL-3. More importantly, T-ALL cell growth and migration were inhibited by small molecule inhibition of PRL-3, suggesting that PRL-3 has potential as a therapeutic target in T-ALL. Taken together, our study identifies PRL-3 as an oncogenic driver in T-ALL both in vitro and in vivo and provides a strong rationale for targeted therapies that interfere with PRL-3 function.

Photon-recoil imaging: Expanding the view of nonlinear x-ray physics.

Addressing the ultrafast coherent evolution of electronic wave functions has long been a goal of nonlinear x-ray physics. A first step toward this goal is the investigation of stimulated x-ray Raman scattering (SXRS) using intense pulses from an x-ray free-electron laser. Earlier SXRS experiments relied on signal amplification during pulse propagation through dense resonant media. By contrast, our method reveals the fundamental process in which photons from the primary radiation source directly interact with a single atom. We introduce an experimental protocol in which scattered neutral atoms rather than scattered photons are detected. We present SXRS measurements at the neon K edge and a quantitative theoretical analysis. The method should become a powerful tool in the exploration of nonlinear x-ray physics.

Effect of dapoxetine on the pharmacokinetics and hemodynamic effects of tamsulosin in men on a stable dose of tamsulosin.

The tolerability of dapoxetine, a short-acting selective serotonin reuptake inhibitor being developed for premature ejaculation, was evaluated when coadministered with tamsulosin. Adult men on a stable dose of tamsulosin were randomized to also receive dapoxetine 30 or 60 mg, or placebo, in a crossover design. Supine and standing vital signs were measured on days 1 and 7. Plasma samples were collected for measurement of tamsulosin, dapoxetine, and dapoxetine metabolites. Coadministration of dapoxetine with tamsulosin did not alter orthostatic profiles or affect the incidence of orthostatic hypotension. Tamsulosin and dapoxetine pharmacokinetics were not altered. Adverse events were reported by 5.4%, 10.9%, and 23.2% of participants receiving tamsulosin with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. The most common adverse events were diarrhea, dizziness, headache, and nausea. Therefore, dapoxetine had no clinically important effects on the pharmacokinetics or orthostatic profile of tamsulosin in men on a stable tamsulosin regimen.

[Extramedullary intradural tuberculosis: a case report and review of the literature]. / Tuberculoma intradural extramedular: descripcion de un caso clinico y revision de la bibliografia.

INTRODUCTION: Central nervous system tuberculosis is a common chronic infection in developing countries, being the most frequent forms: tuberculous meningitis and intracranial tuberculosis. Extramedullary intradural tuberculosis is a rare entity with few cases described in the world literature, and is usually associated with a history of tuberculous meningitis or during antituberculosis treatment. CASE REPORT: A 17 years-old male patient, without history of tuberculosis, with subacute onset and progressive course of compressive myelopathy. Spinal magnetic resonance imaging revealed an intradural extramedullary mass lesion between the C4 and T8 spinal levels. Surgical resection of tuberculoma was realized, followed by chemotherapy. The histopathological study confirmed the diagnostic. CONCLUSIONS: Tuberculosis of the central nervous system is an entity of high incidence in developing countries, and intradural extramedullary tuberculoma should be included in the differential diagnosis of expansive spinal cord injuries, especially if the patient is young and there is a history of pulmonary tuberculosis or tuberculous meningitis. It is also important to take it into account as part of a paradoxical reaction after the initiation of specific treatment. Although surgical resection improves compressive medullary symptoms, medical therapy remains the mainstay in the treatment of tuberculomas.

TITLE: Tuberculoma intradural extramedular: descripcion de un caso clinico y revision de la bibliografia.Introduccion. La tuberculosis del sistema nervioso central es una infeccion cronica comun en paises en vias de desarrollo, y la meningitis tuberculosa y los tuberculomas intracraneales son las formas mas frecuentes. El tuberculoma intradural extramedular es una entidad poco frecuente, con pocos casos descritos en la bibliografia mundial, y por lo general se asocia a un antecedente de meningitis tuberculosa o durante el tratamiento antituberculoso. Caso clinico. Varon de 17 años, sin antecedente de tuberculosis, con cuadro clinico de una mielopatia compresiva de aparicion subaguda y curso progresivo, cuya neuroimagen evidencio una lesion extensa intradural extramedular. Se le realizo cura quirurgica mas laminectomia descompresiva en D4-D8 seguido de quimioterapia. El estudio histopatologico confirmo el diagnostico. Conclusiones. La tuberculosis del sistema nervioso central es una entidad de alta incidencia en nuestro medio, y el tuberculoma intradural extramedular deberia incluirse en el diagnostico diferencial de lesiones expansivas de la medula espinal, mas aun si el paciente es joven y existe el antecedente de tuberculosis pulmonar o meningitis tuberculosa. Asimismo, es importante tenerla en cuenta como parte de una reaccion paradojica despues del inicio del tratamiento especifico. Aunque la reseccion quirurgica mejora los sintomas compresivos medulares, la terapia medica continua siendo el pilar en el tratamiento de los tuberculomas.

Next Generation Driver for Attosecond and Laser-plasma Physics.

The observation and manipulation of electron dynamics in matter call for attosecond light pulses, routinely available from high-order harmonic generation driven by few-femtosecond lasers. However, the energy limitation of these lasers supports only weak sources and correspondingly linear attosecond studies. Here we report on an optical parametric synthesizer designed for nonlinear attosecond optics and relativistic laser-plasma physics. This synthesizer uniquely combines ultra-relativistic focused intensities of about 1020 W/cm2 with a pulse duration of sub-two carrier-wave cycles. The coherent combination of two sequentially amplified and complementary spectral ranges yields sub-5-fs pulses with multi-TW peak power. The application of this source allows the generation of a broad spectral continuum at 100-eV photon energy in gases as well as high-order harmonics in relativistic plasmas. Unprecedented spatio-temporal confinement of light now permits the investigation of electric-field-driven electron phenomena in the relativistic regime and ultimately the rise of next-generation intense isolated attosecond sources.

Using a polymer probe characterized by MALDI-TOF/MS to assess river ecosystem functioning: From polymer selection to field tests.

Characterization of river ecosystems must take into consideration both structural and functional aspects. For the latter, a convenient and simple approach for routine monitoring is based on the decomposition of organic matter measured in terms of breakdown of natural organic substrates like leaf litter, wood sticks. Here we extended the method to a synthetic organic material using polymer probes characterized by MALDI-TOF/MS. We first characterized several commercial available polymers, and finally selected polycaprolactonediol 1250 (PCP 1250), a polyester oligomer, as the most convenient for further studies. PCP 1250 was first tested at mesocosms scale under conditions simulating those of the river, with and without nutrient addition for up to 4weeks. Differences to the starting material measured in terms of changes in the relative ion peak intensities were clearly observed. Ions exhibited a different pattern evolution along time depending on their mass. Greatest changes were observed at longest exposure time and in the nutrient addition treatment. At shorter times, the effect of nutrients (addition or not) was indistinguishable. Finally, we performed an experiment in 11 tributaries of the Ebro River during 97days of exposure. Principal Component Analysis confirmed the different behavior of ions, which were clustered according to their mass. Exposed samples were clearly different to the standard starting material, but could not be well distinguished among each other. Polymer mass loss rates, as well as some environmental variables such as conductivity, temperature and flow were correlated with some peak intensities. Overall, the interpretation of field results in terms of environmental conditions remains elusive, due to the influence of multiple concurrent factors. Nevertheless, breakdown of synthetic polymers opens an interesting field of research, which can complement more traditional breakdown studies to assess river ecosystem functioning.