Additional Treatment Research Articles

Topical dexamethasone decelerates epithelial migration on the canine tympanic membrane.

Epithelial migration (EM) is integral to normal ear structure and function. Glucocorticoids are considered the first-line therapy for various external ear disorders; however, their effects on EM on the tympanic membrane (TM) and the external auditory canal (EAC) are understudied. To test the hypothesis that topical dexamethasone decelerates EM on the TM, this study aimed to evaluate the effects of topical dexamethasone on EM on the TMs of dogs. Seven ears of four healthy dogs. The migration distance of an ink drop deposited on the posterior quadrant of the pars tensa (TM EM rate) of dogs was calculated over 3 weeks from images captured with a video-otoscope. The results were compared by paired Student's t-test to those obtained from a subsequent experiment in which the same dogs were administered a fresh ink drop at the same position as previously (control group), yet additionally administered 0.1% dexamethasone (0.2 mL/ear) daily for the first 14 days (treatment group). One of eight ears was excluded because of an anatomical problem. The TM EM rate of the remaining seven ears decreased by 46.74% in the treatment group compared with the control group (p < 0.05). Topical dexamethasone decelerates EM on the TM of normal dogs' ears. In turn, it is extrapolated that debris removal from the EAC may be slowed, negatively impacting the EAC environment. Consequently, when dogs with otitis receive topical dexamethasone treatment, additional treatment, such as ear canal cleaning, may be required to minimise the effects of impaired TM EM.

An improved method for whole-mount in situ hybridization in regenerating tails of Xenopus laevis tadpoles

Whole-mount in situ hybridization (WISH) is a widely used method that supports the concept of “seeing is believing” by enabling the visualization of gene expression patterns in whole-mount multicellular samples or sections. This technique is essential in the study of epimorphic regeneration in cold-blooded vertebrates, where complex three-dimensional organs such as tails, limbs, and eyes are completely restored after loss. The tadpoles of the frog X. laevis serve as a convenient model for studying regeneration, as they can regenerate their tails within a week after amputation. Modern high-throughput sequencing methods have identified various cell populations involved in the regeneration process and determined the repertoire of genes activated during this time. Specifically, a population of reparative myeloid cells expressing mmp9 as a marker gene has been shown to be crucial for the initial stages of tail regeneration in X. laevis tadpoles. The validation of these data and further examination using WISH offers the advantage of providing detailed information on the spatial and temporal dynamics of target gene expression levels. However, detecting mRNA by WISH can be challenging when mRNA levels are very low, transcripts are localized in hard-to-access areas, or tissue samples are prone to background staining, as is the case with X. laevis regenerating tail samples. Here, we describe additional treatments for regenerating tail samples that minimize background staining and enhance the visualization of cells containing target RNA through in situ hybridization. Using an optimized WISH protocol on X. laevis tadpole tail regenerates, we obtained novel data on the mmp9 expression pattern during the first day post-amputation at the regeneration-competent stage 40 and the regeneration-incompetent stage 47 (refractory period). The significant differences in the expression patterns indicate that mmp9 activity is positively correlated with regeneration competence.

Harnessing Defects in SnSe Film via Photo-Induced Doping for Fully Light-Controlled Artificial Synapse.

2D-layered materials are recognized as up-and-coming candidates to overcome the intrinsic physical limitation of silicon-based devices. Herein, the coexistence of positive persistent photoconductivity (PPPC) and negative persistent photoconductivity (NPPC) in SnSe thin films prepared by pulsed laser deposition provides an excellent avenue for engineering novel devices. It is determined that surface oxygen is co-regulated by physisorption and chemisorption, and the NPPC is attributed to the photo-controllable oxygen desorption behavior. The dominant behavior of chemisorption induces high stability, while physisorption provides room for adjusting NPPC. A simple fully light-modulated artificial synaptic device based on SnSe film is constructed to operate various synaptic plasticity and reversible modulation of conductance by applying 430 and 255nm illuminations. A three-layer artificial neural network structure with a high accuracy of 95.33% to recognize handwritten digital images is implemented based on the device. Furthermore, the pressure-related cognition response of humans while climbing and the foraging and recognition behaviors of anemonefish are mimicked. This work demonstrates the potential of 2D-layered materials for developing neuromorphic computing and simulating biological behaviors without additional treatment. Furthermore, the one-step method for preparation is highly adaptable and expected to realize large-area growth and integration of SnSe-based devices.

The telemedical platform MyaLink for remote monitoring in myasthenia gravis – rationale and protocol for a proof of concept study

Rationale: Myasthenia gravis (MG) is a rare, chronic neurological disorder leading to fluctuating muscle weakness and potentially life-threatening crises. Patients often require life-long specialized treatment, but timely interventions are frequently hindered by the limited availability of specialists. Telemedical solutions at specialized centers enabling patient-physician interaction hold promise in bridging this gap, but are not yet available for MG. We developed ‘MyaLink,’ a remote monitoring platform tailored for MG, and outline the study design assessing the platform and clinical outcomes regarding telemedical intervention. Additionally, we present study results on care-related aspects in MG prior to telemedical intervention to identify challenges in the current care provision process. Design: The platform comprises a patient app and a physician portal, enabling systematic symptom monitoring using data from patient-reported outcome measures (PROMs), coupled devices and a communication module. The randomized controlled study included 45 study participants (SP) over a 12-weeks period, including a group receiving standard care (15 MG patients) and a group with additional telemedical treatment (30 MG patients) including assessment of PROMs, wearable data collection and telemedical check-ups. Questions regarding care-related aspects were assessed at baseline visit. Results: Many SP (N = 33, 73.3%) communicate with the physician managing their MG via email. 73.3% (N = 33) of SP identify areas for improvement in their MG care including symptom monitoring (N = 23, 69.7%), specialist appointment availability (N = 22, 66.7%), medication (N = 22, 66.7%) and specialist accessibility (N = 20, 60.6%). Additionally, 73.3% (N = 33) reported that the effort required to manage their MG was high. Conclusion: Our results emphasize the high demand of affected MG patients for continuous telemedicine services. MyaLink can provide such a service through personalized support based on the exchange of health data. Telemedicine solutions such as MyaLink promise to improve myasthenia care by providing accessible, patient-centred care that enables early detection of worsening symptoms and non-response to treatment. Trial registration: The study was registered under DRKS00029907 on August 19, 2022.

Effect of bifocal soft contact lenses in combination with instillations of the combined drug (Phenylephrine 5% and Tropicamide 0.8%) on the anatomical and functional parameters of the eyes and progression of myopia in pediatric patients

AIM: The study aimed to assess the influence of combined optical and pharmacological effects on the anatomical and functional parameters of the eyes and changes in refraction in pediatric patients with progressive myopia. MATERIAL AND METHODS: Bifocal soft contact lenses (BSCL) Prima BIO Bifocal were prescribed to 43 pediatric patients. At the start of the study, the average age of the children was 10.42±0.26 years, and the average myopia was 3.43±0.19 D. The effect of a combination of optical and medicinal products on the visual apparatus of children was evaluated, namely, bifocal SCLs that form peripheral myopic defocus and instillations of a combined drug containing 0.8% tropicamide and 5% phenylephrine. The combined eye drops, which contained 0.8% tropicamide and 5% phenylephrine, was prescribed once a day at night for 1 month to 23 pediatric patients after wearing the lenses for 1 month (group 1). In group 2 (n=20), patients did not receive any additional treatment, except for optical exposure. RESULTS: The habitual tone of accommodation (HTA) slightly increased after 1 month of using BSCL. In group 1, the HTA decreased to the initial level after 6 and 12 months, whereas it remained high in group 2. Over the year, refraction increased by 0.39 D in group 1 and 0.18 D in group 2 (p 0.05). The annual progression gradient decreased by 2.3 times in group 1 and 5.2 times in group 2. Over the year, the anteroposterior axis increased by 0.13 mm in group 1 and 0.05 mm in group 2. Choroidal thickness increased by 19.09 and 24.77 µm, relative accommodation reserve increased by 0.98 and 1.24 D, and the accommodation amplitude increased by 1.28 and 1.05 D, respectively. CONCLUSION: BSCLs contribute to the reduction of the annual gradient of progression (AGP) and increase in accommodation and choroidal thickness. Instillations of the drug while using BSCL help reduce the habitual tone of accommodation (HTA).

Phytochemicals From Salvia substolonifera With Anti-Angiogenic Properties and Substolide H Decreased Oxygen-Induced Retinal Neovascularization.

Retinal neovascularization is a pathological feature of ischemic retinopathy. Current therapeutic approaches are limited, and additional treatment options are needed. This study aims to discover lead compounds from Salvia substolonifera that inhibit angiogenesis. As a result, an undescribed norditerpene lactone, substolide H (3), and eight known compounds (1, 2, and 4-9) have been isolated. The structure was elucidated using synthetic spectroscopy and electron circular dichroism. Compounds 2, 3, 5, 7, and 9 inhibited human umbilical vein endothelial cells (HUVEC) proliferation with IC50 values of 26.47, 6.10, 43.27, 36.81, and 35.11µM, respectively. Compounds 2, 3, and 7 inhibited HUVEC migration with IC50 values of 12.48, 8.37, and 7.63µM, respectively. Further studies have shown that the substolide H (3) suppresses tube formation in human umbilical vein endothelial cells and that intravitreous administration suppresses retinal neovascularization in oxygen-induced retinopathy mice. Turning to its mechanism of action, we have shown that the anti-angiogenic effect of the substolide H may be through the downregulation of vascular endothelial growth factor expression and the phosphorylation of VEGFR2, ERK1/2, and protein kinase B. Our study represents the first report of these anti-angiogenic compounds from this plant, and substolide H may be a potential candidate for the treatment of retinal neovascularization.

Venous Leak Embolization Results in Clinical Improvement of Patients with Mixed Arterio-Venous Erectile Dysfunction Not Responding to Arterial Revascularization Alone.

To analyze the safety and efficacy of additional venous leak embolization after an initial arterial revascularization to treat patients with combined arteriogenic and venogenic erectile dysfunction (ED). Single-center observational study from October 1, 2019, to September 30, 2022, including 26 patients with ED resistant to phosphodiesterase-5-inhibitors (PDE5i) and without significant clinical benefit after arterial revascularization of erection-related arteries. Additional treatment with venous leak embolization was performed 458 ± 424daysafter arterial revascularization. Arterial obstruction and venous leak were verified based on color Doppler flow analysis, computed tomography angiography, and computed tomography cavernosography. The primary safety endpoint was any major adverse event 6weeks after the procedure. The primary feasibility endpoint was defined as an IIEF-6 (International Index of Erectile Function-6) score improvement of ≥ 4 points at 6-week follow-up post intervention. Procedural success was achieved in all patients with no major adverse events on follow-up. The primary feasibility endpoint at 6-week follow-up was reached with 3/26 (11.5%) of patients following arterial revascularization only. Six weeks after additional venous embolization, the primary feasibility endpoint was reached in 17/26 (65.4%) of patients. Venous leak embolization yields additional clinical improvement and treatment potential in patients with vasculogenic ED not responding to PDE5i due to mixed arterio-venous disease and insufficient clinical improvement after arterial revascularization alone.

Suprachoroidal Triamcinolone Acetonide for Noninfectious Uveitis: Real-World Impact on Clinical Outcomes

PurposeTo evaluate clinically relevant outcomes following suprachoroidal triamcinolone acetonide (TA) injection in eyes with noninfectious uveitis. DesignRetrospective interventional case series. Methods61 eyes (51 patients) who underwent suprachoroidal TA injection between January 1, 2022 and July 1, 2024 were included from a single institution. Main outcome measures included change in central subfield thickness (CST) and best-corrected visual acuity (BCVA) at 6, 12, and 24 weeks in eyes with macular edema and improvement in fluorescein angiography (FA) score at 6 weeks in eyes who underwent FA. Results52 eyes underwent suprachoroidal TA injection for uveitic macular edema. Mean CST improved from 437.61 microns at time of injection to 348.17 microns 6 weeks after (mean difference 89.44 microns, p<0.0001, n = 47). Additional treatment for macular edema was required for 17% (8/48 eyes), 48% (14/29 eyes), and 41% (9/22 eyes) of eyes that returned for follow-up at 6, 12, and 24 weeks, respectively. Of the 17 eyes that returned for follow-up at all visits (6, 12, and 24 weeks), 41.2% (7/17 eyes) did not require any additional treatment during the 24 week follow-up period. 10 eyes underwent FA at time of injection and 6 weeks later. The mean FA score improved from 11.74 to 9.14 (mean difference 2.60, p=0.047). No serious adverse events occurred. ConclusionsSuprachoroidal TA resulted in significant improvement in outcome measures, including central subfield thickness in eyes with macular edema, and leakage on fluorescein angiography, with a favorable side effect profile in real-world clinical practice.

Acute pilonidal abscess: Prospective nationwide audit in the Netherlands.

The aim of this study was to assess Dutch surgical practice and outcomes for acute pilonidal abscess. Patients with pilonidal sinus disease (PSD) who underwent surgical treatment between 1 March 2020 and 1 March 2021 at 36 participating hospitals were included in a prospective observational cohort study. For the present study, only patients with an acute abscess were included for analysis. Outcomes included symptoms, wound healing, time to resume daily activities and complications. Follow-up was 1 year and included questionnaires on recurrent abscesses, symptomatic chronic PSD, quality of life and patient-reported experience measures. Of 681 included patients, 208 presented with an acute pilonidal abscess. Incision and drainage (I&D) was performed in 205 of these patients (99%). The wound healing rate after I&D was 42.2% at the outpatient clinic, with a median time to closure of 43 days. The complication rate was 4.4%. One-year questionnaires were completed by 158 out of 205 patients (77.1%). Fifteen patients (7.3%) had a recurrent abscess within 1 year. The symptomatic chronic PSD rate was 8.8%. Of all the patients presenting with PSD in this prospective national study cohort, 30% had a pilonidal abscess. Incision and drainage showed a low complication rate but successful wound healing in less than half of the patients. The study showed that 91.2% of patients did not undergo additional surgical treatment for symptomatic chronic PSD within 1 year of follow-up.

Effect of Adding Different Concentrations of Mix-Oil Solution to Drinking Water of Broiler Chickens Ross 308 and Breeders at Elevated Temperatures on Blood Biochemical Characteristics and Oxidative Enzymes at the Age of 14 Days

This study was conducted at Al-Anwar Poultry Station located in Babil Governorate for a period of 35 days, from 10/7/2022 to 14/8/2022, to demonstrate the effect of the mix-oil solution added to the drinking water of broiler chickens on some blood biochemical characteristics and oxidation enzymes at the age of 14. day and under conditions of heat stress, where 300 Ross308 broiler chicks were used, one day old, unsexed, and the average weight of the chicks was 40 gm. The mix-oil was added to the drinking water from the first day, as follows: T1: control treatment without addition, T2: adding 0.25 ml of mix-oil / liter of water, T3: adding 0.50 ml of mix-oil / liter of water, T4: adding 0.75 ml of mix-oil / liter of water, T5: Add 1 ml of mix-oil / liter of water. The experimental birds were exposed to periodic temperatures (28-35-28). The most important results we obtained are summarized as follows: A highly significant (p≤0.01) increase in the blood serum glucose concentration of the T5-treated birds compared to the control treatment. A significant increase was also observed (p≤0.01) in the concentration of total protein, albumin and globulin in the T4 treatment compared to the control treatment, while serum cholesterol was observed. The results of our experiment witnessed a "significant" rise and within the normal limits in the concentration of cholesterol for T4-treated birds on T5, T3, and T2 treatments, but it was "significantly similar" in its concentration with the T1 control treatment. The results showed that there was a highly significant increase (p≤0.01) in the rate of triglycerides for the T4 treatment compared to "with all treatments, while high-density lipoproteins (HDL) and low-density lipoproteins (LDL) witnessed a significant decrease (p≤0.01) in all addition treatments compared to" control treatment. There was a "significant" decrease (P≤ 0.01) for all addition treatments in the concentration of ALT enzyme compared to the "control treatment", while the T3 treatment had a significant (P≤ 0.01) superiority in the concentration of AST and GSH-PX enzyme compared with the control treatment, while the concentration of the enzyme CAT value decreased in all addition treatments compared to the control treatment, and the rate of MDA increased in the blood serum of T2 treatment birds compared to the control, which recorded the lowest measured rates, but it did not differ significantly with the T5 treatment in its concentration.

Increasing Wear Resistance of Ploughshare by Electrofriction Treatment

Surface layers of agricultural machinery working bodies are subjected to intensive abrasive wear during operation, which leads to rapid wear of equipment and reduction of its service life. To increase the wear resistance of the working surfaces of tools, the method of induction cladding using ‘Sormait-1’ materials is widely used. However, after coating, additional heat treatment is required, which improves physical and mechanical properties of the material and increases its durability. When using electrofriction technology (EFT) hardening, the surface of the parts is subjected to melting under the influence of electric arcs, which affects the surface characteristics of the coatings. In this work, two types of surface treatment of L53 steel were investigated: induction cladding using ‘Sormait-1’ material, as well as a combination of induction cladding and subsequent electrofriction treatment. The coatings were characterized and compared with the substrate in terms of the following parameters: microstructure, phase composition, hardness distribution, and friction-wear characteristics. After induction cladding of the Sormait-1 material, a dendritic structure was formed; however, subsequent electrofriction treatment resulted in a reduction of this dendritic structure, which contributed to an increase in the hardness of the material. The average hardness of the coatings after electrofriction treatment was 786 HV0.1, which is more than three times the hardness of the substrate. Furthermore, the influence of structural characteristics and hardness on abrasive wear resistance was examined in accordance with ASTM G65 international standards. Field tests were conducted on plough shares before and after electrofriction hardening to evaluate their performance. Each ploughshare was scanned with a structured 3D scanner before and after use in the field. From the scan data, the cutting-edge profile was calculated and three key parameters were determined: linear wear, volumetric wear, and mass reduction. According to the results of field tests, it was found that the service life of the blades hardened by electrofriction technology was 12%–14% higher compared to serial blades processed by induction cladding with the use of ‘Sormait-1’ material. Operational tests of hardened plough shares confirmed the results of laboratory tests and proved the advantages of electrofriction technology for increasing the wear resistance of soil tillage machine working bodies.

Efficacy of Low-Density Lipoprotein Cholesterol Apheresis in the Treatment of Familial Hypercholesterolemia: Single Center Experience.

Familial hypercholesterolemia (FH) is a genetic disorder associated with extremely high levels of low-density lipoprotein cholesterol (LDL-C) and increased incidence of cardiovascular disease. We aimed to evaluate the efficacy and long-term outcomes of lipoprotein apheresis (LA) in the treatment of FH. Cardiovascular events that occurred before and after LA treatment were evaluated by reviewing previous medical records of patients with FH. Thirteen patients (female/male: 8/5) were included in this study. The mean Dutch score was 20±4. All patients were treated with a combination of statin and ezetimibe. Before the onset of LA, 8 patients had a history of coronary artery disease, and the median age at onset of cardiovascular disease (CVD) in these patients was 24 years. At the initiation of LA, the median age was 22 years and the mean LDL-C level was 410±130 mg/dL. The mean duration of LA treatment was 13.9±6.9 years. The mean LDL-C levels before and after the latest three LA treatments were 267±63.4 and 71.5±23.4 mg/dL, respectively. The mean reduction in LDL-C levels after LA was 73±8.2%. De novo cardiovascular events occurred in 10 patients during LA treatment; six of these patients had a known history of CVD before LA. Eight of these patients underwent invasive procedures for therapeutic purposes and the total number of procedures was 12. LA is an effective method of reducing LDL-C levels and an additional treatment option that may slow disease progression in patients with FH who are at high risk of cardiovascular events.

Parotid sialolithiasis - Long term follow-up analyzing surgical approaches.

Present follow-up data comparing transoral and transfacial parotid gland procedures for stone removal to offer insight addressing technical considerations and complications. Retrospective study of a consecutive series of surgical treatments for parotid sialolithiasis from 2013 to 2018 at an academic institution by one surgeon provided review of 16 transoral and 10 transfacial procedures supplemented by long-term follow-up through telephone or mail. Clinical and radiographic parameters, additional treatment, and persistence of symptoms were evaluated. Four of 10 patients treated with the transfacial approach had parotid-cutaneous fistulas addressed with transdermal scopolamine patches and pressure dressings (one also with intraductal steroid infusion) with closure at a median of 12.5 days. A fifth fistula failed to resolve at 23 days and was addressed with parotidectomy. All 8 patients who were contacted (median: 106 months) reported complete resolution of symptoms. None had facial weakness.Six of 16 patients treated by a transoral approach had persistent stone fragments at the conclusion of operation. Four of these 6 patients underwent subsequent procedures (two transoral, one transfacial, one parotidectomy). Among the 11 patients who responded to long-term follow-up (median: 107 months), one reported mild symptoms insufficient to request treatment. Larger stone size coupled with proximal location correlated with the conversion from transoral to include transfacial approach. Patients with retained stone remnants at the conclusion of transoral stone removal are more likely to require additional procedures that result in long-term favorable results. The transfacial approach to stone removal offers long-term favorable results following the common short-term complication of salivary fistula. OCEBM Level 4.

The influence of biostimulations on the yield and quality of Brassica oleracea hybrids in the Non-Chernozem zone of the Russian Federation

Relevance. It is necessary to search for methods for obtaining environmentally friendly products and reducing the pesticide load on agrobiocenoses. Biostimulants can influence the increase in the yield of vegetable crops and improve their quality, which is confirmed by numerous studies. Stimulating effects depend on a combination of various biotic and abiotic factors. The aim of the study was to assess the effect of biostimulants on the yield and quality of Brassica Oleracea in the conditions of the Central Non-Chernozem zone on heavy loamy sod-podzolic soils.Methodology. A field experiment was carried out in the conditions of the Non-Chernozem zone of the Russian Federation on sod-podzolic soil in 2019-2021. In an experiment with two hybrids of Brassica Oleracea: F1 Zarnitsa (mid-early) and F1 Mechta (late-ripening), biostimulants Agrofil and MBK-BIS were studied for soaking seeds, seedlings and foliar treatment. The control variants were without fertilizer (absolute control) and the N90P120K150 background.Results. The effect of mineral fertilizers on both hybrids was characterized by an increase in the weight of heads of cabbage by 11.7 and 23.5%, respectively. When treating seeds, the weight of heads of cabbage increased by 15-18% compared to the background. Additional treatment with stimulants for soaking seedlings in Agrofil and foliar treatment with the MBK-BIS preparation increased the weight of heads of cabbage in comparison with the background in the F1 Zarnitsa hybrid by 21.4 and 23.3%, F1 Mechta - by 21.4 and 25.4%. The contribution of biostimulants to the yield of the used cabbage hybrids is more pronounced in the late-ripening hybrid, which directly depends on the amount of precipitation during the growing season. The studied biostimulants contribute to an increase in the content of vitamin C, fiber, and the amount of sugars in cabbage heads.Conclusion. Biostimulants MBK-BIS and Agrofil are effective for increasing the yield and improving the biochemical composition of the studied Brassica oleracea hybrids in the conditions of the Non-Chernozem zone of Russia.

Top-down predators shape soil bacterial community composition while bottom-up nutrients drive bacterial abundance

Although the top-down and bottom-up concept in microbial food-webs has been a primary interest in ecology, less is still known about it in soil ecosystems. Protists are the primary top-down predators of bacterial communities, altering their compositions, while the bottom-up resources are the primary factors limiting bacterial growth. Here, we hypothesized that the top-down predators modulate soil bacterial community composition, while the bottom-up nutrients control the bacterial growth and population. To precisely control nutrient levels, we used an inert soil substitute consisting of a combination of calcined clay and sand. Nutrients equivalent to the reference paddy field soil were added to microcosms as a control treatment. To investigate the effects of C, N, and P, six additional bottom-up treatments in the absence and double amounts of the nutrients were prepared. Four top-down treatments (no protist addition, Acanthamoeba castellanii, Vermamoeba vermiformis, and Heteromita globosa) were set up for each bottom-up treatment. A total of 252 microcosms under 28 treatments were incubated. Bacterial communities were analyzed using high-throughput sequencing and real-time PCR in the 1st, 3rd, and 5th weeks. The results revealed that the top-down predators significantly altered the bacterial community composition, and the bacterial population was predominantly controlled by the bottom-up nutrients. Analysis of absolute abundance data demonstrated that both top-down and bottom-up factors shaped the bacterial community structure (community composition and population). Random forest analysis classified the amplicon sequence variants associated with the treatments, showing that mostly similar families were affected by both bottom-up and top-down factors. In conclusion, the results of this study fully supported our hypothesis that top-down predators alter community composition, while bottom-up factors influence bacterial population dynamics.

Effect of betahistine on pro-inflammatory cytokine expression in autoimmune inner ear disease and Meniere's disease patients.

Betahistine is a partial H1 receptor agonist and a potent H3 receptor antagonist commonly used for the treatment of MD and peripheral vertigo. The aim of this study was to investigate the impact of betahistine on the salt induced cytokine expression profiles of AIED and MD patients. Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with autoimmune inner ear disease (AIED) or Meniere's disease (MD) during an acute exacerbation of hearing loss. These PBMCs were cultured with 80 mM NaCl or a combination of 80 mM NaCl and betahistine and IL-1β and IL-6 expression were measured by real time PCR and ELISA. In most patients, IL-1β expression in response to NaCl exceeded the unstimulated condition and this expression was abrogated by the addition of betahistine, which was statistically significant at p = .004. mRNA expression of IL-1β was not reduced when samples were treated with both salt and betahistine compared to samples treated with salt alone, inferring the mechanism of betahistine-mediated IL-1β suppression is post-translational. Similarly, IL-6 cellular release was augmented with salt exposure and reduced with co-culture of betahistine. Unlike IL-1 however, betahistine appeared to reduce IL-6 mRNA expression. We observe that betahistine abrogates salt-induced IL-1β expression, suggesting an additional treatment option for AIED and MD patients with inflammatory mediated disease. Level 4.

Snow and nitrogen manipulation do not alter the dominant role of fungi in the N2O production of biocrusts in a temperate desert

The impact of global climate change and human-induced nitrogen (N) deposition on winter weather patterns will have consequences for soil N cycling and greenhouse gas emissions in temperate deserts. Biological soil crusts (referred to as biocrusts) are crucial communities in soil and significant sources of nitrous oxide (N2O) emission in desert ecosystems and are sensitive to environmental changes. The contribution of bacteria and fungi to N2O production in drylands has been acknowledged. However, the effect of changes in snow cover and N deposition on the N2O production of different microbial groups of microorganisms is not yet clear. In this study, we examine the responses of fungi and bacteria mediated pathways involved in soil N2O production from biocrusts to long-term snow cover manipulation and N addition experiments in the Gurbantunggut Desert. These soils were incubated and subjected to biocide treatments (such as cycloheximide and streptomycin, and fungal and bacterial inhibitors), after which rates of potential nitrification and N2O production were measured. Compared with controls, snow removal treatments from bare sand, lichen crust and moss crust reduced background rates of N2O production by 29.41 %, 26.21 % and 20.49 %, respectively; N2O production rates were 1.53-fold higher in bare sand, 1.38-fold higher in lichen crust, and 1.56-fold higher in moss crust after N addition. The addition of streptomycin significantly reduced the potential nitrification rates of bare sand and biocrusts, indicating that bacteria may be important sources of NO3− production in biocrusts rather than fungi. Conversely, fungi were main sources of N2O production in biocrusts. Additionally, fungi also played a major role in N2O production in biocrusts after snow cover manipulation and N addition. Both snow cover manipulation and N addition treatment indirectly affected the N2O production in biocrusts by considerably affecting the content of substrate N and the abundance of microbial groups. Our research suggests that fungi are main contributors for denitrification in biocrusts, and that snow cover changes (removal snow and double snow) and N addition alter the contribution of biotic pathways responsible for N cycling.

Nebulized alteplase in coronavirus disease 2019 pneumonia: a case series

BackgroundMany patients with severe coronavirus disease 2019 pneumonia exhibit signs of microthrombosis. Previous studies discussed intravenous fibrinolytic agents as potential add-on therapy in these patients. Therefore, we propose the inhalative administration of fibrinolytics as a possible safer alternative.Case presentationThis case series describes five white male patients, aged 51–78 years, treated with off-label inhalation of alteplase between November and December 2020. All patients suffered from severe severe acute respiratory syndrome coronavirus 2 infection with respiratory failure. Pulmonary embolism was ruled out by pulmonary angiogram in computed tomography scans, and all patients showed signs of coronavirus disease 2019 pneumonia. Four patients improved clinically, while one patient with advanced chronic diseases died due to multiple organ failure. No directly associated adverse effects were observed following inhalation of alteplase.ConclusionThis case series warrants further attention to investigate inhalative alteplase as an additional treatment in patients with severe coronavirus disease 2019 infection.

Multi-omic network analysis identifies dysregulated neurobiological pathways in opioid addiction

BackgroundOpioid addiction is a worldwide public health crisis. In the United States, for example, opioids cause more drug overdose deaths than any other substance. Yet, opioid addiction treatments have limited efficacy, meaning that additional treatments are needed. MethodsTo help address this problem, we used network-based machine learning techniques to integrate results from genome-wide association studies (GWAS) of opioid use disorder (OUD) and problematic prescription opioid misuse with transcriptomic, proteomic, and epigenetic data from the dorsolateral prefrontal cortex (dlPFC) of opioid overdose victims and controls. ResultsWe identified 211 highly interrelated genes identified by GWAS or dysregulation in the dlPFC of opioid overdose victims that implicated the Akt, BDNF, and ERK pathways, identifying 414 drugs targeting 48 of these opioid addiction-associated genes. Some of the identified drugs are approved to treat other substance use disorders (SUDs) or depression. ConclusionsOur synthesis of multi-omics using a systems biology approach revealed key gene targets that could contribute to drug repurposing, genetics-informed addiction treatment, and future discovery.

Characteristics, treatment patterns and survival of patients with high-risk early hormone receptor-positive breast cancer in French real-world settings: an exploratory study of the CANTO cohort

Patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (HR+ BC) with unfavorable features have an increased risk of relapse and are currently candidate for additional treatment strategies. We evaluated the real-world clinicopathological characteristics, treatment patterns and survival outcomes of these patients within the CANcer TOxicities study (CANTO, NCT01993498). This is a retrospective analysis of the prospective data collected within CANTO between 2012 and 2022. Patients with high-risk HR+ BC were defined either by the identification of at least four positive axillary lymph nodes (LNs) or one to three positive axillary LNs with a tumor size ≥5 cm or histologic grade 3 (cohort 1). The definition 1-3 positive LNs with Ki-67 ≥20% was also considered (cohort 2). The Kaplan-Meier method was used for survival analysis. Patients with high-risk HR+ BC represented 15.0%-19.6% of HR+ BC (cohort 1 and 2, respectively) in the CANTO cohort. Of the 1266 patients in cohort 1, 617 patients (49.0%) had ≥4 LNs, 327 (26.0%) had tumor ≥5 cm and 727 (57.6%) had grade III tumors. 79.9% had a favorable Charlson comorbidity score and 88.1% stage II/IIIA. Patients with ≥10 LNs accounted for 11.8%. (Neo)adjuvant chemotherapy was administered in 94.2%. Endocrine therapy was prescribed in 97.3%, mostly with aromatase inhibitors and discontinued in 34.3%, mainly for adverse events. Patients enrolled at least 6 years before data extraction had a 5-year invasive disease-free survival and 5-year distant relapse-free survival of 79.9% [95% confidence interval (CI) 77.2% to 82.4%] and 83.5% (95% CI 80.9% to 85.7%), respectively. This real-world study confirms that patients with HR+ BC and unfavorable clinicopathological features are at risk of relapse early in their adjuvant treatment trajectory, despite (neo)adjuvant chemotherapy. It is imperative to implement innovative treatment approaches for high-risk patients, ideally adding them as early as possible to the adjuvant treatment.