Antagonism between neuropeptides and monoamines in a distributed circuit for pathogen avoidance.

Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to the pathogenic bacterium Pseudomonas aeruginosa PA14, the nematode Caenorhabditis elegans modifies its sensory preferences to avoid the pathogen. Here, we identify antagonistic neuromodulators that shape this acquired avoidance behavior. Using an unbiased cell-directed neuropeptide screen, we show that AVK neurons upregulate and release RF/RYamide FLP-1 neuropeptides during infection to drive pathogen avoidance. Manipulations that increase or decrease AVK activity accelerate or delay pathogen avoidance, respectively, implicating AVK in the dynamics of avoidance behavior. FLP-1 neuropeptides drive pathogen avoidance through the G protein-coupled receptor DMSR-7, as well as other receptors. DMSR-7 in turn acts in multiple neurons, including tyraminergic/octopaminergic neurons that receive convergent avoidance signals from the cytokine DAF-7/transforming growth factor ß. Neuromodulators shape pathogen avoidance through multiple mechanisms and targets, in agreement with the distributed neuromodulatory connectome of C. elegans.

Revisional Robotic Bariatric Surgery. Largest Single Centre Prospective Cohort Study and Review of the Literature.

Introduction: Robotic bariatric surgery (RBS) has seen a surge in popularity in recent years, yet questions persist about its utility concerning postoperative complications, costs, and technical aspects. RBS, while increasing in number, presents a greater technical challenge associated with more post-operative complications compared to primary bariatric surgery. In this study, we present our single institution experience and review the literature to assess the value of robotic revisional surgery. Material and Method: The retrospective review involved 42 patients (31 females, 11 males) who underwent various procedures, with the most frequent being the conversion of sleeve gastrectomy to gastric bypass (n=30). Encouragingly, no leaks or severe complications were identified. Furthermore, a systematic review indicated comparable outcomes, with decreased complication rates favoring robotic revisional surgery. Results: In direct comparison to standard laparoscopic revisional bariatric surgery, revisional robotic surgery demonstrated superior results in terms of efficacy, safety, and reduced hospital stay. However, rates of mortality, morbidity, and reintervention did not significantly differ between the two approaches. Conclusions: Considering these findings, we advocate for surgeons to acquire proficiency in the robotic technique, as part of the broader process of democratization and standardization of bariatric surgery. Embracing revisional robotic bariatric surgery can lead to improved patient outcomes, and its wider implementation may lead to enhanced surgical care and patient satisfaction in the field of bariatric procedures.

An Integrated Pump-Controlled Variable Coupler Fabricated by Ultrafast Laser Writing.

The design and fabrication of a integrated symmetric directional coupler dependent o the pumping power and operating at a 1534 nm wavelength is reported. The twin-core waveguide was inscribed into Er3+/Yb3+ co-doped phosphate glass by a femtosecond laser direct writing technique. By optical pumping, the coupling ratio can be modulated due to the changes induced in the refractive index of the material. The experimental results demonstrated that the coupling ratio can be tuned continuously from 100/0 to 50/50 by increasing the pump's power from 0 to 350 mW. The developed twin-core coupler has promising applications for on-chip all-optical signal processing and communication systems.

Influence of Heat Accumulation on Morphology Debris Deposition and Wetting of LIPSS on Steel upon High Repetition Rate Femtosecond Pulses Irradiation.

The fabrication of laser-induced periodic surface structures (LIPSS) over extended areas at high processing speeds requires the use of high repetition rate femtosecond lasers. It is known that industrially relevant materials such as steel experience heat accumulation when irradiated at repetition rates above some hundreds of kHz, and significant debris redeposition can take place. However, there are few studies on how the laser repetition rate influences both the debris deposition and the final LIPSS morphology. In this work, we present a study of fs laser-induced fabrication of low spatial frequency LIPSS (LSFL), with pulse repetition rates ranging from 10 kHz to 2 MHz on commercially available steel. The morphology of the laser-structured areas as well as the redeposited debris was characterized by scanning electron microscopy (SEM) and µ-Raman spectroscopy. To identify repetition rate ranges where heat accumulation is present during the irradiations, we developed a simple heat accumulation model that solves the heat equation in 1 dimension implementing a Forward differencing in Time and Central differencing in Space (FTCS) scheme. Contact angle measurements with water demonstrated the influence of heat accumulation and debris on the functional wetting behavior. The findings are directly relevant for the processing of metals using high repetition rate femtosecond lasers, enabling the identification of optimum conditions in terms of desired morphology, functionality, and throughput.

Optical Properties of 2D Micro- and Nanostructures of ZnO:K.

ZnO nano- and microstructures doped with K were grown by the Vapor-Solid method. Wires and needles are the main morphology observed, although some structures in the form of ribbons and triangular plates were also obtained. Besides these, ball-shaped structures which grow around a central wire were also detected. Raman and cathodoluminescence investigations suggest that variations in morphology, crystalline quality and luminescence emissions are related to the different lattice positions that K occupies depending on its concentration in the structures. When the amount is low, K ions mainly incorporate as interstitials (Ki), whereas K occupies substitutional positions of Zn (KZn) when the amount of K is increased. Electron Backscattered Diffraction shows that ribbons and triangular plates are oriented in the (0001) direction, which indicates that the growth of this type of morphologies is related to distortions introduced by the Ki since this position favors the growth in the (0001) plane. In the case of the ball-shaped structures, the compositional analysis and Raman spectra show that they consist of K2SO4. Finally, the capability of the elongated structures to act as waveguides and optical resonators was investigated. Due to the size of the K ion, practically double that of the Zn, and the different positions it can adopt within the ZnO lattice (Ki or KZn), high distortions are introduced that compromise the resonators performance. Despite this, quality factor (Q) and fineness (F) show acceptable values (80 and 10 at 544 nm, respectively), although smaller than those reported for doping with smaller size alkali, such as Li.

Single-Step Fabrication of High-Performance Extraordinary Transmission Plasmonic Metasurfaces Employing Ultrafast Lasers.

Plasmonic metasurfaces based on the extraordinary optical transmission (EOT) effect can be designed to efficiently transmit specific spectral bands from the visible to the far-infrared regimes, offering numerous applications in important technological fields such as compact multispectral imaging, biological and chemical sensing, or color displays. However, due to their subwavelength nature, EOT metasurfaces are nowadays fabricated with nano- and micro-lithographic techniques, requiring many processing steps and carrying out in expensive cleanroom environments. In this work, we propose and experimentally demonstrate a novel, single-step process for the rapid fabrication of high-performance mid- and long-wave infrared EOT metasurfaces employing ultrafast direct laser writing. Microhole arrays composing extraordinary transmission metasurfaces were fabricated over an area of 4 mm2 in timescales of units of minutes, employing single pulse ablation of 40 nm thick Au films on dielectric substrates mounted on a high-precision motorized stage. We show how by carefully characterizing the influence of only three key experimental parameters on the processed micro-morphologies (namely, laser pulse energy, scan velocity, and beam shaping slit), we can have on-demand control of the optical characteristics of the extraordinary transmission effect in terms of transmission wavelength, quality factor, and polarization sensitivity of the resonances. To illustrate this concept, a set of EOT metasurfaces having different performances and operating in different spectral regimes has been successfully designed, fabricated, and tested. Comparison between transmittance measurements and numerical simulations has revealed that all the fabricated devices behave as expected, thus demonstrating the high performance, flexibility, and reliability of the proposed fabrication method. We believe that our findings provide the pillars for mass production of EOT metasurfaces with on-demand optical properties and create new research trends toward single-step laser fabrication of metasurfaces with alternative geometries and/or functionalities.

Competition Effects during Femtosecond Laser Induced Element Redistribution in Ba- and La-Migration Based Laser Written Waveguides.

Fs-laser induced element redistribution (FLIER) has been a subject of intensive research in recent years. Its application to various types of glasses has already resulted in the production of efficient optical waveguides, tappers, amplifiers and lasers. Most of the work reported on FLIER-based waveguides refers to structures produced by the cross-migration of alkali (Na, K) and lanthanides (mostly La). The latter elements act as refractive index carrying elements. Herein, we report the production of Ba-based, FLIER-waveguides in phosphate glass with an index contrast > 10-2. Phosphate glasses modified with the same amount of Na2O and K2O, and variable amounts of BaO and/or La2O3 were used to produce the FLIER-waveguides with Ba and or La acting as index carriers. Ba-only modified glasses show a waveguide writing threshold and light guiding performance comparable to that of La-based structures. However, mixed Ba-La glasses show a much higher element migration threshold, and much smaller compositionally modified regions. This behavior is consistent with a competition effect in the cross-migration of both elements (Ba and La) against the alkalis. Such an effect can be applied to inhibit undesired element redistribution effects in fs-laser processing applications in multicomponent glasses.

Femtosecond laser induced thermophoretic writing of waveguides in silicate glass.

Here in, the fs-laser induced thermophoretic writing of microstructures in ad-hoc compositionally designed silicate glasses and their application as infrared optical waveguides is reported. The glass modification mechanism mimics the elemental thermal diffusion occurring in basaltic liquids at the Earth's mantle, but in a much shorter time scale (108 times faster) and over a well-defined micrometric volume. The precise addition of BaO, Na2O and K2O to the silicate glass enables the creation of positive refractive index contrast upon fs-laser irradiation. The influence of the focal volume and the induced temperature gradient is thoroughly analyzed, leading to a variety of structures with refractive index contrasts as high as 2.5 × 10-2. Two independent methods, namely near field measurements and electronic polarizability analysis, confirm the magnitude of the refractive index on the modified regions. Additionally, the functionality of the microstructures as waveguides is further optimized by lowering their propagation losses, enabling their implementation in a wide range of photonic devices.

Preferential Growth of ZnO Micro- and Nanostructure Assemblies on Fs-Laser-Induced Periodic Structures.

In this work, we demonstrate the use of laser-induced periodic surface structures (LIPSS) as templates for the selective growth of ordered micro- and nanostructures of ZnO. Different types of LIPSS were first produced in Si-(100) substrates including ablative low-frequency spatial (LSF) LIPSS, amorphous-crystalline (a-c) LIPSS, and black silicon structures. These laser-structured substrates were subsequently used for depositing ZnO using the vapor-solid (VS) method in order to analyze the formation of organized ZnO structures. We used scanning electron microscopy and micro-Raman spectroscopy to assess the morphological and structural characteristics of the ZnO micro/nano-assemblies obtained and to identify the characteristics of the laser-structured substrates inducing the preferential deposition of ZnO. The formation of aligned assemblies of micro- and nanocrystals of ZnO was successfully achieved on LSF-LIPSS and a-c LIPSS. These results point toward a feasible route for generating well aligned assemblies of semiconductor micro- and nanostructures of good quality by the VS method on substrates, where the effect of lattice mismatch is reduced by laser-induced local disorder and likely by a small increase of surface roughness.

Role of the La/K Compositional Ratio in the Properties of Waveguides Written by Fs-Laser Induced Element Redistribution in Phosphate-Based Glasses.

The local modification of the composition of glasses by high repetition femtosecond laser irradiation is an attractive method for producing photonic devices. Recently, the successful production of waveguides with a refractive index contrast (Δn) above 10-2 by fs-laser writing has been demonstrated in phosphate glasses containing La2O3 and K2O modifiers. This large index contrast has been related to a local enrichment in lanthanum in the light guiding region accompanied by a depletion in potassium. In this work, we have studied the influence of the initial glass composition on the performance of waveguides that are produced by fs-laser induced element redistribution (FLIER) in phosphate-based samples with different La and K concentrations. We have analyzed the contribution to the electronic polarizability of the different glass constituents based on refractive index measurements of the untreated samples, and used it to estimate the expected index contrast caused by the experimentally measured local compositional changes in laser written guiding structures. These estimated values have been compared to experimental ones that are derived from near field images of the guided modes with an excellent agreement. Therefore, we have developed a method to estimate before-hand the expected index contrast in fs-laser written waveguides via FLIER for a given glass composition. The obtained results stress the importance of considering the contribution to the polarizability of all the moving species when computing the expected refractive index changes that are caused by FLIER processes.

Alternative switching strategies based on regimens with a low genetic barrier: do clinicians have a choice nowadays?

Clinicians sometimes use switching strategies based on regimens such as RAL + ABC/3TC or RPV + ABC/3TC in order to resolve tolerability or safety issues associated with conventional recommended first-line strategies. Despite the low genetic barrier of these regimens, high safety and efficacy rates have been reported in retrospective studies.

Síntesis de biomateriales, pruebas de biocompatibilidad in vitro, primeros pasos en ingeniería tisular en Bolivia / Synthesis of biomaterials, in vitro biocompatibility tests, first steps in tissular engineering in Bolivia

El desarrollo de biomateriales bioactivos como andamios para la osteointegración o regeneración de tejidos ha dado grandes pasos, el presente trabajo, muestra los procesos de síntesis de biomateriales como la hidroxiapatita, biomateriales del sistema SiO2-CaO-P2O5-Al2O3 y biovidrios del sistema SiO2.Li2O, se ha logrado caracterizar los biomateriales obtenidos, con resultados similares a los de otros investigadores por técnicas con la Difracción de Rayos X y la Microscopía Electrónica de Barrido, se ha evaluado su comportamientoen pruebas de biocompatibilidad y bioactividad en soluciones de Plasma Rico en Factores de Crecimiento y Fluido corporal simulado, seguidamente y con el fin de evaluar la incorporación de sustancias antibacteriales se ha dopado uno de ellos con plata, logrando determinar que el material tiene esta capacidad, estos resultados son los primeros pasos para encarar posteriores trabajos en el campo de la Ingeniería Tisular en Bolivia, y de esta forma encarar procesos de ostointegración y regeneración de tejidos en general.

The development of bioactive biomaterials as scaffolds for osseointegration or tissue regeneration has taken great steps, the present work shows the synthesis processes of biomaterials such as hydroxyapatite, biomaterials of the SiO2-CaO-P2O5-Al2O3 system and bio-libraries of the SiO2 system. Li2O, it has been possible to characterize the biomaterials obtained, with results similar to those of other researchers by techniques with X-ray Diffraction and Scanning Electron Microscopy, their behavior in biocompatibility and bioactivity tests in Plasma Rico solutions has been evaluated in Growth factors and simulated body fluid, then and in order to evaluate the incorporation of antibacterial substances, one of them has been doped with silver, managing to determine that the material has this capacity, these results are the first steps to face further work in the field of Tissue Engineering in Bolivia, and thus face Osteintegration processes and tissue regeneration in general.

Biomimetic surface structures in steel fabricated with femtosecond laser pulses: influence of laser rescanning on morphology and wettability.

The replication of complex structures found in nature represents an enormous challenge even for advanced fabrication techniques, such as laser processing. For certain applications, not only the surface topography needs to be mimicked, but often also a specific function of the structure. An alternative approach to laser direct writing of complex structures is the generation of laser-induced periodic surface structures (LIPSS), which is based on directed self-organization of the material and allows fabrication of specific micro- and nanostructures over extended areas. In this work, we exploit this approach to fabricate complex biomimetic structures on the surface of steel 1.7131 formed upon irradiation with high repetition rate femtosecond laser pulses. In particular, the fabricated structures show similarities to the skin of certain reptiles and integument of insects. Different irradiation parameters are investigated to produce the desired structures, including laser repetition rate and laser fluence, paying special attention to the influence of the number of times the same area is rescanned with the laser. The latter parameter is identified to be crucial for controlling the morphology and size of specific structures. As an example for the functionality of the structures, we have chosen the surface wettability and studied its dependence on the laser processing parameters. Contact angle measurements of water drops placed on the surface reveal that a wide range of angles can be accessed by selecting the appropriate irradiation parameters, highlighting also here the prominent role of the number of scans.

Controlling the Wettability of Steel Surfaces Processed with Femtosecond Laser Pulses.

The wettability of a material surface is an essential property that can define the range of applications it can be used for. In the particular case of steel, industrial applications are countless but sometimes limited because of the lack of control over its surface properties. Although different strategies have been proposed to tune the wetting behavior of metal surfaces, most of them require the use of processes such as coatings with different materials or plasma/chemical etching. In this work, we present two different laser-based direct-write strategies that allow tuning the wetting properties of 1.7131 steel over a wide range of contact angles using a high repetition rate femtosecond laser. The strategy consists in the writing of parallel and crossed lines with variable spacing. A detailed morphological analysis confirmed the formation of microstructures superimposed with nanofeatures, forming a hierarchical surface topography that influences the wetting properties of the material surface. Contact angle measurements with water confirm that this behavior is mostly dependent on the line-to-line spacing and the polarization-dependent orientation of the structures. Moreover, we demonstrate that the structures can be easily replicated in a polymer using a laser-fabricated steel master, which enables low-cost mass production. These findings provide a practical route for developing user-defined wetting control for new applications of steel and other materials functionalized by rapid laser structuring.

Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study.

BACKGROUND: Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. DESIGN: Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. METHODS: We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy. RESULTS: The study population comprised 467 patients. Median age was 49 years (IQR: 45-53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/µL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician's criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4-99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 [95%CI, 16.9-24.2]). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician's decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks. CONCLUSIONS: Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.

Author Correction: Coherent scatter-controlled phase-change grating structures in silicon using femtosecond laser pulses.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Infliximab Biosimilars: A Promising but Unusual Treatment for Mycobacterial Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Patients.

Immune reconstitution inflammatory syndrome can present as a paradoxical reaction after initiation of antiretroviral treatment in patients with severe immunosuppression and underlying infections. Immune reconstitution inflammatory syndrome has often been associated with mycobacteria, and the clinical response to traditional treatment with corticosteroids is not always satisfactory. Consequently, administration of an infliximab biosimilar could lead to an improvement in the clinical status of these patients.

Coherent scatter-controlled phase-change grating structures in silicon using femtosecond laser pulses.

Periodic structures of alternating amorphous-crystalline fringes have been fabricated in silicon using repetitive femtosecond laser exposure (800 nm wavelength and 120 fs duration). The method is based on the interference of the incident laser light with far- and near-field scattered light, leading to local melting at the interference maxima, as demonstrated by femtosecond microscopy. Exploiting this strategy, lines of highly regular amorphous fringes can be written. The fringes have been characterized in detail using optical microscopy combined modelling, which enables a determination of the three-dimensional shape of individual fringes. 2D micro-Raman spectroscopy reveals that the space between amorphous fringes remains crystalline. We demonstrate that the fringe period can be tuned over a range of 410 nm - 13 µm by changing the angle of incidence and inverting the beam scan direction. Fine control over the lateral dimensions, thickness, surface depression and optical contrast of the fringes is obtained via adjustment of pulse number, fluence and spot size. Large-area, highly homogeneous gratings composed of amorphous fringes with micrometer width and millimeter length can readily be fabricated. The here presented fabrication technique is expected to have applications in the fields of optics, nanoelectronics, and mechatronics and should be applicable to other materials.

Three-Dimensional Self-Organization in Nanocomposite Layered Systems by Ultrafast Laser Pulses.

Controlling plasmonic systems with nanometer resolution in transparent films and their colors over large nonplanar areas is a key issue for spreading their use in various industrial fields. Using light to direct self-organization mechanisms provides high-speed and flexible processes to meet this challenge. Here, we describe a route for the laser-induced self-organization of metallic nanostructures in 3D. Going beyond the production of planar nanopatterns, we demonstrate that ultrafast laser-induced excitation combined with nonlinear feedback mechanisms in a nanocomposite thin film can lead to 3D self-organized nanostructured films. The process, which can be extended to complex layered composite systems, produces highly uniform large-area nanopatterns. We show that 3D self-organization originates from the simultaneous excitation of independent optical modes at different depths in the film and is activated by the plasmon-induced charge separation and thermally induced NP growth mechanisms. This laser color marking technique enables multiplexed optical image encoding and the generated nanostructured Ag NPs:TiO2 films offer great promise for applications in solar energy harvesting, photocatalysis, or photochromic devices.

Correction: Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study.

[This corrects the article DOI: 10.1371/journal.pone.0164455.].