Clues for facial canal dehiscence in chronic otitis media

Introduction and objectives: The goal of this study was to determine the impact of external and middle ear findings in the incidence of facial canal dehiscence (FCD) during mastoidectomy for chronic otitis media.Material and methodsWe examined the operative details of 186 patients who underwent primary tympanomastoidectomy for chronic otitis media between January 2015 and January 2020 retrospectively.In this study we only evaluated the second portion of the facial nerve canal.ResultsThe global prevalence of FCD was 22.6% (42/186 patients) with a higher incidence, of 38.7% (36/93), in patients with chronic otitis media with cholesteatoma (C-COM).Associations were found between facial canal dehiscence, labyrinthine fistula (p˂ .001) and facial nerve paralysis (p˂ .001).Ossicular erosions were observed at a significant level in patients with facial canal dehiscence, the incidence of FCD was significantly higher (p=.005, Odds ratio 5.489) when malleus and incus were eroded, incus plus stapes were eroded (p=.014; OR 4.059) and malleus, incus, and stapes together were eroded (p=.002; OR 4.929).ConclusionsThis study revealed an incidence of facial canal dehiscence of 22.6%. It also revealed that the presence of lateral semicircular canal fistula is associated with a higher prevalence of facial canal dehiscence.The same was noted in the case of some ossicular erosions, especially the combinations of eroded malleus and incus, incus and stapes, and all 3 ossicles. (AU)

Introducción y objetivos: El objetivo de este estudio fue determinar el impacto de los hallazgos del oído externo y medio en la incidencia de dehiscencia del canal facial (DCF) durante la mastoidectomía por otitis media crónica.Material y métodosExaminamos los detalles quirúrgicos de 186 pacientes intervenidos de timpanomastoidectomía primaria por otitis media crónica entre enero de 2015 y enero de 2020 de forma retrospectiva.En este estudio solo evaluamos la segunda porción del canal del nervio facial.ResultadosLa prevalencia global de DCF fue del 22,6% (42/186 pacientes) con una incidencia mayor, del 38,7% (36/93), en pacientes con otitis media crónica con colesteatoma (C-COM).Se encontraron asociaciones entre DCF, fístula laberíntica (p ˂ 0,001) y parálisis del nervio facial (p ˂ 0,001).Se observaron erosiones osiculares significativas en pacientes con DCF. La incidencia de DCF fue significativamente mayor (p=0,005; odds ratio 5.489) cuando el martillo y el yunque estaban erosionados, el yunque y el estribo erosionados (p=0,014; OR 4,059) y erosiones del martillo, yunque y estribo juntos (p=0,002; OR 4,929).ConclusionesEste estudio reveló una incidencia de DCF del 22,6%. También reveló que la presencia de fístula del canal semicircular lateral se asocia con una mayor prevalencia de DCF.Lo mismo se observó en el caso de algunas erosiones osiculares, especialmente las combinaciones de martillo y yunque, yunque y estribo, y los 3 huesecillos erosionados. (AU)

Parkinson's Disease Symptoms Associated with Developing On-State Axial Symptoms Early after Subthalamic Deep Brain Stimulation.

Background: The relationship between axial symptoms in Parkinson's disease (PD) and subthalamic deep brain stimulation (STN-DBS) is still unclear. Purpose: We searched for particular clinical characteristics before STN-DBS linked to on-state axial problems after surgery. Methods: We retrospectively analyzed baseline motor, emotional and cognitive features from PD patients with early axial symptoms (within 4 years after STN-DBS) and late axial symptoms (after 4 years). We also considered a group of PD patients without axial symptoms for at least 4 years after surgery. Results: At baseline, early-axial PD patients (n = 28) had a higher on-state Unified Parkinson's Disease Rating Scale III (15.0 ± 5.6 to 11.6 ± 6.2, p = 0.020), higher axial score (2.4 ± 1.8 to 0.7 ± 1.0, p < 0.001) and worse dopaminergic response (0.62 ± 0.12 to 0.70 ± 0.11, p = 0.005), than non-axial PD patients (n = 51). Early-axial PD patients had short-term recall impairment, not seen in non-axial PD (36.3 ± 7.6 to 40.3 ± 9.3, p = 0.041). These variables were similar between late-axial PD (n = 18) and non-axial PD, but late-axial PD showed worse frontal dysfunction. Conclusions: PD patients with early axial symptoms after DBS may have a significantly worse presurgical motor phenotype, poorer dopaminergic response and memory impairment. This may correspond to a more severe form of PD.

Continuous subcutaneous apomorphine infusion in the early phase of advanced Parkinson's disease: A prospective study of 22 patients.

INTRODUCTION: Parkinson's disease (PD) patients usually start treatment with apomorphine infusion (APO) in later stages of advanced PD (aPD). This timing limits the evaluation of its motor efficacy and other potential clinical benefits throughout the full course of aPD. METHODS: We prospectively analyzed the effect of APO on motor and non-motor symptoms, cognitive function and quality of life (QoL) in 22 PD patients with early stage aPD, defined as: age < 71 years and diagnosis of aPD for < 3 years. RESULTS: At baseline, mean (±SD) age and disease duration were 59.4 ± 6.1 and 8.7 ± 3.5 years, respectively. After 6 months of APO treatment, daily off-time decreased from 4.98 ± 2.37 to 1.48 ± 1.47 h (p ≤ 0.001) and UPDRS IV scores from 7.00 ± 2.58 to 5.32 ± 2.48 (p = 0.018). Dyskinesia did not worsen with APO despite an overall increase in levodopa equivalent daily dose. Mean NMSS scores improved with APO, from 52.50 ± 27.24 to 38.68 ± 27.17 (p = 0.002), with particular improvements in apathy and sleep quality. Mean PDQ-39 score was reduced with APO from 31.96 ± 11.93 to 19.27 ± 11.86 (p ≤ 0.001). Overall, cognition did not change after APO, while slight improvements were observed in executive functioning (attention and planning). All but one patient eventually underwent subthalamic deep brain stimulation. CONCLUSION: In patients with early stage initial aPD, s substantial benefit of APO was observed on motor symptoms, driven by a 70% reduction in off-time versus baseline, superior to that observed in previous prospective studies. APO also improved frontal dysfunction in PD patients.

Continuous Subcutaneous Apomorphine Infusion before Subthalamic Deep Brain Stimulation: A Prospective, Comparative Study in 20 Patients.

BACKGROUND: Studies comparing the clinical efficacy of apomorphine infusion (APO) with subsequent subthalamic deep brain stimulation (STN-DBS) in advanced Parkinson's disease (aPD) are currently lacking. Retrospective data have shown that patients treated with APO are usually older, have a more prolonged disease, and a more severe phenotype. OBJECTIVE: To compare the benefit of APO with that of STN-DBS on motor, non-motor, cognitive, and quality of life in the same patient when given sequentially. METHODS: We prospectively analyzed 20 aPD patients over 3 different treatment phases: baseline (optimized medical treatment), during APO treatment, and during subsequent STN-DBS treatment. The APO and STN-DBS phases were stable for 6 months, and evaluation of the different treatments was separated by 6 months. RESULTS: Compared to baseline, APO, and STN-DBS reduced mean daily off time by 70.5% and 89.3% (P = 0.012), respectively, and scores for Unified Parkinson's Disease Rating Scale (UPDRS) IV by 27.5% and 80.5% (P ≤ 0.001), Non-motor symptoms scale (NMSS) by 24.6% and 49.3% (P ≤ 0.001), Montgomery Asberg depression scale (MADRS) by 7.4% and 39.0% (P = 0.27), Starkstein apathy scale (SAS) by 51.1% and 39.9% (P = 0.734), Parkinson's disease sleep scale 2 (PDSS-2) by 25.7% and 56.7% (P ≤ 0.001), and Parkinson's disease questionnaire 39 item (PDQ-39) by 39.6% and 64.9% (P ≤ 0.001). Global cognition did not change with either therapy, but phonetic fluency worsened after STN-DBS compared to APO (P = 0.022). CONCLUSIONS: Both APO and STN-DBS improved motor and non-motor symptoms and quality of life compared to optimized medical treatment in aPD. Overall, STN-DBS was the most effective treatment, but APO showed a pronounced benefit on motor symptoms. Effective treatment for aPD should not be delayed, even when waiting for surgery.

Can flowers affect land surface albedo and soil microclimates?

The phenology of vegetation, namely leaf-out and senescence, can influence the Earth's climate over regional spatial scales and long time periods (e.g., over 30 years or more), in addition to microclimates over local spatial scales and shorter time periods (weeks to months). However, the effects of flowers on climate and microclimate are unknown. We investigate whether flowers can influence light reflected by the land surface and soil microclimate in a subalpine meadow. We conducted a flower removal experiment with a common sunflower species, Helianthella quinquenervis, for 3 years (2015, 2017, and 2019). The flower removal treatment simulates the appearance of the meadow when Helianthella flowers earlier under climate change and loses its flowers to frost (other plant structures are not damaged by frost). We test the hypotheses that a reduction in cover of yellow flowers leads to a greener land surface, lower reflectance, warmer and drier soils, and increased plant water stress. Flower removal plots are greener, reflect less light, exhibit up to 1.2 °C warmer soil temperatures during the warmest daylight hours, and contain ca. 1% less soil moisture compared to controls. However, soils were warmer in only 2 of the 3 years, when flower abundance was high. Helianthella water use efficiency did not differ between removal and control plots. Our study provides evidence for a previously undocumented effect of flowers on soil microclimate, an effect that is likely mediated by climate change and flowering phenology. Many anthropogenic environmental changes alter landscape albedo, all of which could be mediated by flowers: climate change, plant invasions, and agriculture. This study highlights how further consideration of the effects of flowers on land surface albedo could improve our understanding of the effects of vegetation on microclimate.

Genetic Material Manipulation and Modification by Optical Trapping and Nanosurgery-A Perspective.

Light can be employed as a tool to alter and manipulate matter in many ways. An example has been the implementation of optical trapping, the so called optical tweezers, in which light can hold and move small objects with 3D control. Of interest for the Life Sciences and Biotechnology is the fact that biological objects in the size range from tens of nanometers to hundreds of microns can be precisely manipulated through this technology. In particular, it has been shown possible to optically trap and move genetic material (DNA and chromatin) using optical tweezers. Also, these biological entities can be severed, rearranged and reconstructed by the combined use of laser scissors and optical tweezers. In this review, the background, current state and future possibilities of optical tweezers and laser scissors to manipulate, rearrange and alter genetic material (DNA, chromatin and chromosomes) will be presented. Sources of undesirable effects by the optical procedure and measures to avoid them will be discussed. In addition, first tentative approaches at cellular-level genetic and organelle surgery, in which genetic material or DNA-carrying organelles are extracted out or introduced into cells, will be presented.

Fluorescent redox-dependent labeling of lipid droplets in cultured cells by reduced phenazine methosulfate.

Natural and synthetic phenazines are widely used in biomedical sciences. In dehydrogenase histochemistry, phenazine methosulfate (PMS) is applied as a redox reagent for coupling reduced coenzymes to the reduction of tetrazolium salts into colored formazans. PMS is also currently used for cytotoxicity and viability assays of cell cultures using sulfonated tetrazoliums. Under UV (340 nm) excitation, aqueous solutions of the cationic PMS show green fluorescence (λem: 526 nm), whereas the reduced hydrophobic derivative (methyl-phenazine, MPH) shows blue fluorescence (λem: 465 nm). Under UV (365 nm) excitation, cultured cells (LM2, IGROV-1, BGC-1, and 3T3-L1 adipocytes) treated with PMS (5 µg/mL, 30 min) showed cytoplasmic granules with bright blue fluorescence, which correspond to lipid droplets labeled by the lipophilic methyl-phenazine. After formaldehyde fixation blue-fluorescing droplets could be stained with oil red O. Interestingly, PMS-treated 3T3-L1 adipocytes observed under UV excitation 24 h after labeling showed large lipid droplets with a weak green emission within a diffuse pale blue-fluorescing cytoplasm, whereas a strong green emission was observed in small lipid droplets. This fluorescence change from blue to green indicates that reoxidation of methyl-phenazine to PMS can occur. Regarding cell uptake and labeling mechanisms, QSAR models predict that the hydrophilic PMS is not significantly membrane-permeant, so most PMS reduction is expected to be extracellular and associated with a plasma membrane NAD(P)H reductase. Once formed, the lipophilic and blue-fluorescing methyl-phenazine enters live cells and mainly accumulates in lipid droplets. Overall, the results reported here indicate that PMS is an excellent fluorescent probe to investigate labeling and redox dynamics of lipid droplets in cultured cells.

Optoelectronic generation of bio-aqueous femto-droplets based on the bulk photovoltaic effect.

The generation and manipulation of small aqueous droplets is an important issue for nano- and biotechnology, particularly, when using microfluidic devices. The production of very small droplets has been frequently carried out by applying intense local electric fields to the fluid, which requires power supplies and metallic electrodes. This procedure complicates the device and reduces its versatility. In this work, we present a novel and flexible, to the best of our knowledge, electrodeless optoelectronic method for the production of tiny droplets of biologically friendly aqueous fluids. Our method takes advantage of the photoinduced electric fields generated by the bulk photovoltaic effect in iron-doped lithium niobate crystals. Two substrate configurations, presenting the polar ferroelectric axis either parallel or perpendicular to the active surface, have been successfully tested. In both crystal geometries, small droplets on the femtoliter scale have been obtained, although with a different spatial distributions correlated with the symmetry of the photovoltaic fields. The overall results demonstrate the effectiveness of the optoelectronic method to produce femtoliter droplets, both with pure water and with aqueous solutions containing biological material.

Plasmonic Hot-Electron Reactive Oxygen Species Generation: Fundamentals for Redox Biology.

For decades, the possibility to generate Reactive Oxygen Species (ROS) in biological systems through the use of light was mainly restricted to the photodynamic effect: the photoexcitation of molecules which then engage in charge- or energy-transfer to molecular oxygen (O2) to initiate ROS production. However, the classical photodynamic approach presents drawbacks, like per se chemical reactivity of the photosensitizing agent or fast molecular photobleaching due to in situ ROS generation, to name a few. Recently, a new approach, which promises many advantages, has entered the scene: plasmon-driven hot-electron chemistry. The effect takes advantage of the photoexcitation of plasmonic resonances in metal nanoparticles to induce a new cohort of photochemical and redox reactions. These metal photo-transducers are considered chemically inert and can undergo billions of photoexcitation rounds without bleaching or suffering significant oxidative alterations. Also, their optimal absorption band can be shape- and size-tailored in order to match any of the near infrared (NIR) biological windows, where undesired absorption/scattering are minimal. In this mini review, the basic mechanisms and principal benefits of this light-driven approach to generate ROS will be discussed. Additionally, some significant experiments in vitro and in vivo will be presented, and tentative new avenues for further research will be advanced.

Polirradiculoneuropatía desmielinizante inflamatoria crónica asociada al tratamiento con infusión intraduodenal de levodopa-carbidopa / Chronic inflammatory demyelinating polyradiculoneuropathy associated with treatment using intraduodenal infusion of levodopa-carbidopa

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Optical Tweezers: Phototoxicity and Thermal Stress in Cells and Biomolecules.

For several decades optical tweezers have proven to be an invaluable tool in the study and analysis of myriad biological responses and applications. However, as with every tool, they can have undesirable or damaging effects upon the very sample they are helping to study. In this review the main negative effects of optical tweezers upon biostructures and living systems will be presented. There are three main areas on which the review will focus: linear optical excitation within the tweezers, non-linear photonic effects, and thermal load upon the sampled volume. Additional information is provided on negative mechanical effects of optical traps on biological structures. Strategies to avoid or, at least, minimize these negative effects will be introduced. Finally, all these effects, undesirable for the most, can have positive applications under the right conditions. Some hints in this direction will also be discussed.

Photothermal effect by 808-nm laser irradiation of melanin: a proof-of-concept study of photothermal therapy using B16-F10 melanotic melanoma growing in BALB/c mice.

The photothermal effect is undergoing great interest due to advances in new photosensitizing materials and better-suited light sources, but studies are frequently hampered by the need to employ exogenous photothermal agents and expensive irradiation devices. Here we present a simple strategy based on direct NIR irradiation of the melanin pigment with a commercial 808-nm laser pointer. Proof-of-concept studies showed efficient photothermal effects on melanin in vitro and in vivo. After NIR irradiation, BALB/c mice bearing B16-F10 melanotic melanoma tumors revealed severe histopathological damage and massive necrosis in melanin-containing tumor tissue, while surrounding healthy tissues showed no damage. Therefore, the feasibility of this approach may allow implementing direct procedures for photothermal therapy of pigmented tumors.

Continuous subcutaneous apomorphine in advanced Parkinson's disease patients treated with deep brain stimulation.

INTRODUCTION: Deep brain stimulation (DBS) is an effective therapy for patients with advanced Parkinson's disease (PD). However, sometimes, it is not sufficient to adequately control motor symptoms. We describe our experience with continuous subcutaneous apomorphine infusion (APO) in patients with DBS. METHODS: We undertook a retrospective analysis of all patients treated with DBS and APO at our centre over 12 years. Subjects were allocated to four groups: (1) APO temporarily before DBS, (2) APO after DBS complications before a new DBS, (3) APO after definitive DBS removal, and (4) APO in patients with DBS and declining response. Motor state and other parameters were analysed and compared for the different treatments. RESULTS: Data for 71 patients were evaluated. Group 1: (n = 18) patients improved their motor function significantly with both APO and DBS (off-hours before APO 5.4 ± 1.4; after APO 1.4 ± 1.2, p > 0.001; after DBS 0.7 ± 0.8, p < 0.001). Group 2: (n = 11) patients were found to have mild but significant worsening of motor state between the first DBS treatment (off-hours 0.7 ± 1.0) and APO (2.2 ± 1.5, p = 0.02), and improvement between APO and the second DBS treatment (off-hours 0.6 ± 0.8, p = 0.03). Group 3: (n = 12) patients had mild but significant worsening of motor function between DBS (off-hours 1.1 ± 1.0) and APO (2.0 ± 0.9, p = 0.03). Group 4: (n = 13) significant improvement in motor function was observed between DBS alone (off-hours 3.9 ± 2.6) and DBS combined with APO (2.2 ± 1.3, p = 0.03). CONCLUSION: In advanced PD, DBS may be not sufficient or may fail to control motor symptoms adequately. In these cases, APO, whether alone or in combination with DBS, is a good choice to improve the disease control.

Cell cycle modulation through subcellular spatially resolved production of singlet oxygen via direct 765 nm irradiation: manipulating the onset of mitosis.

Reactive oxygen species, ROS, are acknowledged signaling molecules in cellular processes. Singlet molecular oxygen, O2(a1Δg), is one ROS that can initiate cell responses that range from death to proliferation. To better understand the mechanisms involved, it is necessary to further investigate cell response to the "dose" of O2(a1Δg) that has been selectively produced at the expense of other ROS. In this context, dose refers not just to the amount of O2(a1Δg) produced, but also to the subcellular spatial domain in which it is produced. In this study, we selectively produced small and non-toxic amounts of O2(a1Δg) in sensitizer-free experiments by irradiating oxygen at 765 nm using a laser focused either into the nucleus or cytoplasm of HeLa cells. We find that O2(a1Δg)-mediated cell proliferation depends appreciably on the site of O2(a1Δg) production. At the same incident laser power, irradiation into the cytoplasm elicits moderate enhancement of proliferation, whereas irradiation into the nucleus leads to an appreciable delay in the onset and completion of mitosis. We discuss these results in light of what is known about the intracellular photophysics of O2(a1Δg) and the redox state of different cell domains.

Instauración ambulatoria y manejo inicial del tratamiento con infusión intraduodenal de levodopa-carbidopa en la enfermedad de Parkinson avanzada / Outpatient establishment and initial management of treatment with intraduodenal levodopa-carbidopa infusion in advanced Parkinson's disease

Introducción. El tratamiento con infusión intraduodenal de levodopa-carbidopa es una de las tres terapias de que disponemos en la actualidad en la enfermedad de Parkinson avanzada. Optimiza el beneficio del tratamiento antiparkinsoniano al contrarrestar el efecto negativo que provoca el vaciado gástrico errático sobre la absorción de la levodopa oral. El objetivo es describir nuestro protocolo de instauración del tratamiento de modo ambulatorio. Pacientes y métodos. En nuestra unidad hemos implementado un protocolo de instauración del tratamiento con infusión continua de levodopa-carbidopa intestinal sin necesidad de ingreso hospitalario gracias al desarrollo de un circuito multidisciplinar entre el propio servicio de neurología, la unidad de endoscopia digestiva y la unidad de hospitalización a domicilio. Resultados. En año y medio se trató a cinco pacientes con enfermedad de Parkinson avanzada. Todos ellos continúan con el tratamiento y no han tenido complicaciones significativas. Conclusión. La instauración ambulatoria del tratamiento ahorra costes y evita el impacto negativo del ingreso en el paciente con enfermedad de Parkinson avanzada, de la misma manera que favorece su adaptación y tolerancia a aquél

Introduction. Treatment with intraduodenal levodopa-carbidopa infusion is one of the three therapies currently available for advanced Parkinson's disease. It optimizes the benefit of antiparkinsonian treatment by counteracting the negative effect of erratic gastric emptying on the absorption of oral levodopa. The purpose is to describe our outpatient protocol of treatment establishment. Patients and methods. In our unit we have implemented a protocol for the treatment with intradoudenal levodopacarbidopa infusion without admission based on the development of a multidisciplinary circuit among the Neurology Service, the Digestive Endoscopy Unit and the Home Hospitalization Unit. Results. Over one and a half year, we treated five patients with advanced Parkinson's disease. All of them remain on the medication and no significant side effect has taken place. Conclusion. The outpatient onset install of this treatment saves costs and avoids the negative impact of admission on the patient with advanced Parkinson's disease, in the same way that favors their adaptation and tolerability to it

Fluorescent in vivo imaging of reactive oxygen species and redox potential in plants.

Reactive oxygen species (ROS) are by-products of aerobic metabolism, and excessive production can result in oxidative stress and cell damage. In addition, ROS function as cellular messengers, working as redox regulators in a multitude of biological processes. Understanding ROS signalling and stress responses requires methods for precise imaging and quantification to monitor local, subcellular and global ROS dynamics with high selectivity, sensitivity and spatiotemporal resolution. In this review, we summarize the present knowledge for in vivo plant ROS imaging and detection, using both chemical probes and fluorescent protein-based biosensors. Certain characteristics of plant tissues, for example high background autofluorescence in photosynthetic organs and the multitude of endogenous antioxidants, can interfere with ROS and redox potential detection, making imaging extra challenging. Novel methods and techniques to measure in vivo plant ROS and redox changes with better selectivity, accuracy, and spatiotemporal resolution are therefore desirable to fully acknowledge the remarkably complex plant ROS signalling networks.

Tetrazolium salts and formazan products in Cell Biology: Viability assessment, fluorescence imaging, and labeling perspectives.

For many years various tetrazolium salts and their formazan products have been employed in histochemistry and for assessing cell viability. For the latter application, the most widely used are 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and 5-cyano-2,3-di-(p-tolyl)-tetrazolium chloride (CTC) for viability assays of eukaryotic cells and bacteria, respectively. In these cases, the nicotinamide-adenine-dinucleotide (NAD(P)H) coenzyme and dehydrogenases from metabolically active cells reduce tetrazolium salts to strongly colored and lipophilic formazan products, which are then quantified by absorbance (MTT) or fluorescence (CTC). More recently, certain sulfonated tetrazolium, which give rise to water-soluble formazans, have also proved useful for cytotoxicity assays. We describe several aspects of the application of tetrazolium salts and formazans in biomedical cell biology research, mainly regarding formazan-based colorimetric assays, cellular reduction of MTT, and localization and fluorescence of the MTT formazan in lipidic cell structures. In addition, some pharmacological and labeling perspectives of these compounds are also described.