Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Subcutaneous Lipoatrophy and Skin Depigmentation Secondary to TMJ Intra-Articular Corticosteroid Injection.

Chronic orofacial pain is a complex multidimensional experience that produces disability and impairment of normal mandibular function. Overall estimations of chronic orofacial pain prevalence are 7 to 11% of the general population. Temporomandibular disorders (TMDs) are one of the most prevalent chronic orofacial pain conditions, with temporomandibular joint (TMJ) arthralgia accounting for 30.1% of TMD patients. Interventional procedures are often used in pain and palliative medicine to achieve reasonable and cost-effective pain relief. The use of intra-articular corticosteroids in relieving arthralgia and improving joint function has been well documented. We present the clinical case of an 84-year-old female patient who presented to the Hospital del Salvador orofacial pain service with preauricular pain, limited range of motion, provoked pain at palpation, and decreased function in the preauricular region. In accordance with the DC/TMD criteria, left TMJ arthralgia and degenerative joint disease was diagnosed and was later corroborated by cone beam computed tomography. An intra-articular injection of 10 mg of methylprednisolone was prescribed, and the patient underwent the procedure in accordance with Hospital del Salvador's intra-articular injection protocol. The patient underwent the intervention without any inconvenience. At the 3-week follow-up visit, the patient presented with a depigmented depression zone adjacent to the site of injection. After echotomography, we concluded that the patient had developed skin depigmentation and subcutaneous lipoatrophy related to the intra-articular injection of methylprednisolone. To the best of our knowledge, this is the first report of this complication secondary to an interventional procedure in the TMJ. Clinicians should be aware of, and patients must be advised of, this rare complication before an intra-articular intervention.

Allowing New Opportunities in Advanced Laparoscopy Training Using a Full High-Definition Training Box.

INTRODUCTION: Simulated laparoscopy training is limited by its low-quality image. A high-definition (HD) laparoscopic training box was developed under the present necessity of simulating advanced surgery. OBJECTIVE: To describe and test a new HD laparoscopic training box for advanced simulation training. METHODS: We describe the features and image quality of the new training box. The simulator was tested and then evaluated by a group of 76 expert surgeons using a 4-item questionnaire. To assess the effectiveness of training using this simulation box, 15 general surgery residents were trained to perform a laparoscopic jejuno-jejunostomy in a validated simulation program. They were assessed with objective rating scales before and after the training program, and their results were compared with that of experts. RESULTS: The training box was assembled using high-density fiberglass shaped as an insufflated abdomen. It has an adapted full-HD camera with a LED-based illumination system. A manually self-regulated monopod attached to the camera enables training without assistance. Of the expert surgeons who answered the questionnaire, 91% said that the simulation box had a high-quality image and that it was very similar to real laparoscopy. All residents trained improved their rating scores significantly when comparing their initial versus final assessment ( P < .001). Their performance after completing the training in the box was similar to that of experts ( P > .2). CONCLUSIONS: This novel laparoscopic training box presents a high-resolution image and allows training different types of advanced laparoscopic procedures. The simulator box was positively assessed by experts and demonstrated to be effective for laparoscopy training in resident surgeons.

Impact of SARS-CoV-2 infection on pain crisis and acute chest syndrome in patients with sickle cell anemia: A retrospective multi-cohort study based on US national data from 2020 to 2022.

COVID-19 infection has been a significant contributor to global morbidity and mortality, especially among those patients with chronic diseases. The Centers for Disease Control and Prevention have classified sickle cell disease (SCD) as a condition that increases the risk of severe illness from COVID-19 infection. A retrospective study was conducted using the TRiNetX health research network database to identify SCA patients ( HbSS, Sbeta-thalassemia zero) who had SARS-CoV-2 infection over 2 years; these were compared with similar patients who did not have the infection in terms of demographics, pain control, and laboratory parameters COVID-19 illness impacts [ain crises and ACS, and prior vaccination against influenza and COVID-19 may represent a protective factor for developing pain crises.

Computer Simulation of Three-Phase Equilibria for Some Water/n-Alkane Binary Systems.

In this work, the vapor-liquid-liquid equilibrium (VLLE) of the water/n-pentane, water/n-hexane, water/n-octane, and water/n-decane binary systems is calculated by computer simulation using the NVT-Gibbs ensemble (in the version of three simulation boxes) combined with the configurational bias Monte Carlo method. The combination of both methods, the molecular potential models used, and the simulation details allowed us to calculate the triphasic equilibrium properties of the systems studied: the densities of the three phases in equilibrium, their compositions, and potential energies. In previous works, these simulations were not carried out at a temperature range nor water/n-alkanes systems simulated in this work, probably because they are highly nonideal systems; so, to the best of our knowledge, this is the first time that this phenomenon is studied in detail. The results from VLLE simulations of the water/n-pentane system for temperatures from 343.2 to 435 K, the water/n-hexane system for temperatures from 373.11 to 473.15 K, the water/n-octane system for temperatures from 310.9 to 500 K, and for the water/n-decane system for temperatures from 374.15 to 525 K are reported here. The temperature range was selected in concordance with the experimental data available for an adequate study of the VLLE simulation results. The subcritical densities (vapor and liquid rich in n-alkane phases) at various temperatures fit well with the scaling law and the law of rectilinear diameters, allowing the estimation of upper critical end point temperature and density of the VLLE. The simulation results show a good prediction with experimental data reports in the literature.

[Characterization of peripheral blood cellular populations in relation to Ascaris Lumbricoides infection in rural areas of Bolívar]. / Caracterización de poblaciones celulares en sangre periférica, con relación a la infección por Ascaris lumbricoides en zonas rurales de Bolívar.

OBJECTIVE: To compare the relative frequencies of immune cell populations in the peripheral blood according to A. lumbricoides infection status. METHODS: Peripheral blood samples were collected from participants infected (n = 35) and uninfected with A. lumbricoides (n=27) residing in different rural municipalities of Bolívar. Infection was diagnosed using two coprological examinations and the Kato-Katz technique. Immunophenotyping was performed using two panels of markers and staining in fresh blood. The flow cytometry reading was performed on a spectral cytometer (Northern Lights, Cytek, USA). The populations identified in the first panel (Figure 1) were T lymphocytes (CD45+ CD3+), CD4+ or CD8+, B lymphocytes (CD45+ SSClow CD3- CD19+), neutrophils (CD45+ SSChi CD3- CD16+), and eosinophils (CD45+ SSChi CD3- CD16low). Monocytes were identified in another panel (Figure 2): classical (CD14++ CD16 -), intermediate (CD14++ CD16+), and non-classical (CD14+ CD16++). Dendritic cells, including CD123 + + CD303 + (plasmacytoid), HLA-DR + + CD1c + (myeloid CD1c +), and CD14-CD141 + + (myeloid CD141 +), were also identified. The study received approval from the Ethics Committee of the University of Cartagena, and participants provided informed consent. Funding was provided by the Colombian Sistema General de Regalías under BPIN2020000100405 - BPIN2020000100364. RESULTS: No significant differences were observed in age [mean cases: 35.69 (SD: 17.7) vs. controls: 37.04 (SD: 15.6) years] or sex (cases: 62.9% vs. controls: 74.1%) (Table 1). All infections were mild, with a median of 96 eggs (IQR, 48-216). A marginally significant difference was observed only in the percentage of neutrophils (45.37% in cases vs. 54.79% in controls, p=0.041) (Figure 3). Although the frequency of eosinophils was higher in the cases (8.1% vs. 6%), this difference was not significant (p=0.138) (Figure 3). No significant differences were observed in the populations of monocytes or dendritic cells between cases and controls (Figure 4). CONCLUSION: Mild A. lumbricoides infection appears to affect the number of neutrophils in peripheral blood. The low infection intensity in the studied samples may explain the lack of a significant impact on other cellular populations.

OBJETIVO: Comparar las frecuencias relativas de poblaciones de células inmunes en sangre periférica de acuerdo con el estado de infección por A. lumbricoides. MÉTODOS: Se recolectaron muestras de sangre periférica de participantes infectados (n=35) y no infectados con A. lumbricoides (n=27), residentes en distintos municipios rurales de Bolívar. La infección se diagnosticó por dos métodos coprológicos y la técnica de Kato-Katz. El inmunofenotipo se determinó con dos baterías de marcadores y tinciones en sangre fresca. La lectura fue realizada en un citómetro espectral (Northern Lights, Cytek, USA). Las poblaciones identificadas en la primera batería (Figura 1) fueron linfocitos T (CD45+ CD3+) CD4+ o CD8+, linfocitos B (CD45+ SSClow CD3- CD19+), neutrófilos (CD45+ SSChi CD3- CD16+), y eosinófilos (CD45+ SSChi CD3- CD16low). Los monocitos se identificaron en otra batería (Figura 2): clásicos (CD14++ CD16­), intermedios (CD14++ CD16+), y no clásicos (CD14+ CD16++). También se identificaron células dendríticas, tales como: CD123++ CD303+ (plasmocitoides), HLA-DR++ CD1c+ (mieloides CD1c+), y CD14- CD141++ (mieloides CD141+). El estudio recibió la aprobación del Comité de Ética de la Universidad de Cartagena, y los participantes otorgaron su consentimiento informado. La financiación fue proporcionada por el Sistema General de Regalías de Colombia, bajo el BPIN2020000100405 - BPIN2020000100364. RESULTADOS: No se observaron diferencias significativas en edad [media = casos: 35,69 (DE: 17,7) vs controles: 37,04 (DE: 15,6 años] o sexo (casos: 62,9% vs. controles: 74,1%). Todas las infecciones fueron leves con una mediana de huevos de 96 (RIC: 48 - 216). Solo se encontró diferencia significativa marginal en el porcentaje de neutrófilos (45,37% en los casos vs 54,79% en controles, p=0,041). Si bien la frecuencia de eosinófilos fue más alta en los casos (8,1% vs. 6%), esta diferencia no alcanzó la significancia (p=0,138). No se observaron diferencias significativas en las poblaciones de monocitos o células dendríticas entre casos y controles (Figura 4). CONCLUSIÓN: La infección leve por A. lumbricoides parece afectar el número de neutrófilos en sangre periférica. Es posible que por la baja intensidad de la infección en la muestra estudiada, no se detecte un impacto importante de la misma sobre el resto de las poblaciones celulares. Palabras claves: Helmintos; Ascaris lumbricoides; Citometría de flujo; Inmunofenotipado; Neutrófilos.

Navigated intraoperative ultrasound in neuro-oncology: volumetric accuracy and correlation with high-field MRI.

OBJECTIVE: The use of intraoperative techniques to detect residual tumors has recently become increasingly important. Intraoperative MRI has long been considered the gold standard; however, it is not widely used because of high equipment costs and long acquisition times. Consequently, real-time intraoperative ultrasound (ioUS), which is much less expensive than MRI, has gained popularity. The aim of the present study was to evaluate the capacity of ioUS to accurately determine the primary tumor volume and detect residual tumors. METHODS: A prospective study of adult patients who underwent surgery for intra-axial brain tumors between November 2017 and October 2020 was performed. Navigated intraoperative ultrasound (nioUS) of the brain was used to guide tumor resection and to detect the presence of residual disease. Both convex (5-8 MHz) and linear array (6-13 MHz) probes were used. Tumor volume and residual disease were measured with nioUS and compared with MR images. A linear regression model based on a machine learning pipeline and a Bland-Altman analysis were used to assess the accuracy of nioUS versus MRI. RESULTS: Eighty patients (35 females and 45 males) were included. The mean age was 58 years (range 25-80 years). A total of 88 lesions were evaluated; there were 64 (73%) gliomas, 19 (21.6%) metastases, and 5 (5.7%) other tumors, mostly located in the frontal (41%) and temporal (27%) lobes. Most of the tumors (75%) were perfectly visible on ioUS (grade 3, Mair grading system), except for those located in the insular lobe (grade 2). The regression model showed a nearly perfect correlation (R2 = 0.97, p < 0.001) between preoperative tumor volumes from both MRI and nioUS. Ultrasonographic visibility significantly influenced this correlation, which was stronger for highly visible (grade 3) tumors (p = 0.01). For residual tumors, the correlation between postoperative MRI and nioUS was weaker (R2 = 0.78, p < 0.001) but statistically significant. The Bland-Altman analysis showed minimal bias between the two techniques for pre- and postoperative scenarios, with statistically significant results for the preoperative concordance. CONCLUSIONS: The authors' findings show that most brain tumors are well delineated by nioUS and almost perfectly correlated with MRI-based measurements both pre- and postoperatively. These data support the hypothesis that nioUS is a reliable intraoperative technique that can be used for real-time monitoring of brain tumor resections and to perform volumetric analysis of residual disease.

Structure factor and rheology of chain molecules from molecular dynamics.

Equilibrium and non-equilibrium molecular dynamics were performed to determine the relationship between the static structure factor, the molecular conformation, and the rheological properties of chain molecules. A spring-monomer model with Finitely Extensible Nonlinear Elastic and Lennard-Jones force field potentials was used to describe chain molecules. The equations of motion were solved for shear flow with SLLOD equations of motion integrated with Verlet's algorithm. A multiple time scale algorithm extended to non-equilibrium situations was used as the integration method. Concentric circular patterns in the structure factor were obtained, indicating an isotropic Newtonian behavior. Under simple shear flow, some peaks in the structure factor were emerged corresponding to an anisotropic pattern as chains aligned along the flow direction. Pure chain molecules and chain molecules in solution displayed shear-thinning regions. Power-law and Carreau-Yasuda models were used to adjust the generated data. Results are in qualitative agreement with rheological and light scattering experiments.

A monster into the heart: an unusual presentation of cardiac leiomyosarcoma.

BACKGROUND: Malignant primary cardiac tumors are infrequent and can lead to an unfavorable prognosis if not identified and treated promptly. Early detection and prompt treatment of malignant primary cardiac tumors are crucial for a better prognosis. This article presents a case of primary cardiac leiomyosarcoma and reviews the literature on this topic. CASE PRESENTATION: Female patient that developed recurrent pericardial effusion and hemodynamic instability caused by a cardiac tumor, later identified as leiomyosarcoma. Multidisciplinary treatment was administered to the patient. CONCLUSIONS: The initial approach to this type of pathology should include multimodality imaging to establish a prompt diagnosis leading to complete standard treatment, to minimize risks to the patient's heart function which may include resection with complete margins of the neoplasm, otherwise the prognosis may be poor.

[Soy beverages and women's health: evidence review and experts opinion]. / Bebidas de soja y salud femenina. Revisión de la evidencia y opinión de expertos.

Introduction: Soy drinks are an increasingly consumed option within the Western diet. However, there are concerns about potential endocrine disruptor effects and possible impact on women's reproductive health. This review evaluates scientific documents in gynecology and obstetrics under an evidence-based medicine approach. All methods adhered to PRISMA 2020 declaration guidelines. The evaluated studies do not support a positive association between soy intake and early puberty or breast cancer; instead, a protective effect against such neoplasm was observed. Transplacental passage of soy isoflavones and their presence in breast milk has been reported without any maternal-fetal complications nor congenital malformations. Exposure to soy-derived products appears to have a neutral effect on body weight and bone health. Studies performed in adults indicate that soy may promote a minimal increase in thyrotropin (TSH) in subjects with subclinical hypothyroidism. The impact of soy-based foods on gut microbiota appears favorable, especially when consuming fermented products. Many of the human studies have been conducted with isoflavones supplements, isolated or textured soy proteins. Therefore, the results and conclusions should be interpreted cautiously, as these are not entirely applicable to commercial soy beverages.

Introducción: Las bebidas vegetales de soja constituyen una alternativa dentro de la dieta habitual. Sin embargo, existe la preocupación de potenciales efectos en la salud reproductiva de la mujer por mecanismos de disrupción endócrina. En esta revisión se evalúan documentos científicos en el área de la Ginecología y la Obstetricia bajo el tamiz de la medicina basada en la evidencia, respondiendo preguntas estructuradas. La metodología se apegó a las guías establecidas por la declaración PRISMA 2020. Los estudios evaluados descartan un riesgo incrementado de pubertad precoz o cáncer de mama; incluso se aprecia un efecto protector frente a dicha neoplasia. Se ha reportado el paso transplacentario de isoflavonas de soja y su presencia en la leche materna, sin que ello implique una relación con complicaciones materno-fetales o malformaciones congénitas. La exposición a productos de soja no parece influir sobre el peso corporal y la salud ósea de la mujer. Los estudios en adultos indican que la soja favorece un mínimo incremento de tirotropina (TSH) en personas con antecedente de hipotiroidismo subclínico. El impacto de los alimentos basados en soja sobre la microbiota intestinal parece ser favorable para su diversidad, particularmente al consumir productos fermentados. Muchos de los estudios en humanos han sido realizados con suplementos de isoflavonas o con productos que contienen proteínas aisladas o texturizadas de soja. Por tanto, los resultados y las conclusiones deben interpretarse con cautela ya que no son totalmente extrapolables a las bebidas comerciales de soja.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Costa Rica's Marine Protected Areas: status and perspectives.

With 51 100km2 of terrestrial area and 589 000km2 of national waters, Costa Rica is considered one of the countries with the greatest biodiversity. It has approximately 3.5% of the world marine species. In the last four decades, Costa Rica has done a considerable effort to create a representative system of Protected Areas (PA), mainly terrestrial. We present an assessment of the current situation of the Marine Protected Areas (MPA) in Costa Rica, through an historical analysis, and an evaluation of their distribution, coverage and management categories. Costa Rica has 166 protected areas covering 50% of the coastline; of these 20 are MPAs, classified as National Parks (90.6%), National Wildlife Refuges (6.6%), Wetlands (1.5%), Biological Reserves (1%), and one Absolute Natural Reserve (0.3%). According to IUCN criteria, 93.7% correspond to category II, 5% to IV and 1.3% to I. The marine protected surface is 5 296.5km2, corresponding to 17.5% of the territorial waters and 0.9% of the Exclusive Economic Zone. The median distance between MPAs is 22.4km in the Pacific and 32.9km along the Caribbean. The median size is close to 54km2. The main threats to MPAs are the lack of coordination between governmental agencies, limited economic resources, restricted patrolling and control, poor watershed management, and rampant coastal alteration.

Hematologic manifestations of coronavirus disease 2019 in children: Case-series report and a review.

On 11 March 2020, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) was declared as a pandemic by the World Health Organization (WHO). As the COVID-19 pandemic has ravaged worldwide, children have not been unaffected. Information gleaned from adult experience with the disease has aided in disease detection and treatment strategies in children. Numerous cases have been described in adult literature about hematologic manifestations of COVID-19. This case series aims to report several hematologic presentations in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C, an immune-mediated reaction leading to severe COVID-19 illness) with and without a primary hematologic disorder.

Developing a Digital Technology System to Address COVID-19 Health Needs in Guatemala: A Scientific Diaspora Case Study.

Scientific diasporas are organized groups of professionals who work together to contribute to their country of origin. Since the start of the COVID-19 pandemic in 2020, scientific diasporas around the world have focused their efforts to support the public health response in their countries of origin. As the first cases of COVID-19 were reported in Guatemala in March of 2020, a team of four Guatemalan nationals, residing abroad and in-country, started collaborating to tackle COVID-19 misinformation and issues with healthcare services navigation. Their collaboration was facilitated by FUNDEGUA, a Guatemalan nonprofit, which provided a legal framework to establish partnerships and fundraise. The team created a digital technological system called ALMA (Asistente de Logística Médica Automatizada in Spanish). A female character named ALMA was created to personify the digital information services, through social media profiles, an interactive website, a free national multilingual call center, and an artificial intelligence-based chatbot. More members joined the nascent interdisciplinary diaspora through professional/personal references or social media. ALMA provided a platform for Guatemalan nationals to contribute with their skillset to their country during a global crisis through flexible schedules and short- or long-term involvement. As the team grew, the services for query resolution and information dissemination expanded as well. The ALMA initiative shows that scientific diasporas can provide an avenue for professionals to contribute to Guatemala, regardless of their residence and job commitments.

Pocillopora spp. growth analysis on restoration structures in an Eastern Tropical Pacific upwelling area.

Coral reefs in Culebra Bay (North Pacific of Costa Rica) are threatened by multiple anthropogenic disturbances including global warming, overfishing, eutrophication, and invasive species outbreaks. It is possible to assist their recovery by implementing ecological restoration techniques. This study used artificial hexagonal steel structures, called "spiders" to compare growth of Pocillopora spp. coral fragments of different sizes. Three initial fragment class sizes were used: 2, 5 and 8 cm, with each class size having 42 initial fragments. Changes in fragment length, width and area were measured monthly from January to December 2020. Results showed an overall survivorship of 70.21%, and no significant differences in survivorship and linear growth rate were detected between class sizes. The linear growth rates are 4.49 ± 1.19 cm year-1, 5.35 ± 1.48 cm year-1 and 3.25 ± 2.22 cm year-1 for the 2, 5 and 8 cm initial class sizes, respectively. Our results do not show significant differences in growth rates between the different initial fragment sizes. However, since small fragments (2 cm) present higher mortality during the first month, we recommend using larger fragments. In addition, coral fragments grew 48% more during the non-upwelling season, which may suggest that it might be more effective and safer to start the restoration efforts during this period.

Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea.

Kanamycin and cisplatin are ototoxic drugs. The mechanisms are incompletely known. With subcutaneous kanamycin (400 mg/kg, 15 days), auditory threshold shifts were detected at days 12-13 at 16 and 32 kHz, extending to 8 and 4 kHz at days 14-15. The outer hair cell (OHC) loss was concentrated past day 12. The maximum cochlear length showing apoptotic cells, tested with TUNEL, was at day 13. At day 15, 1/5 of the apical cochlea contained preserved OHCs. 3-nitrotyrosine (3-NT) immunolabeling, showing oxidative stress, was found in surviving OHCs and in basal and middle portions of the stria vascularis (SV). The antioxidant Gpx1 gene expression was decreased. The immunocytochemistry showed diminished Gpx1 in OHCs. With intraperitoneal cisplatin (16 mg/kg, single injection), no evoked auditory activity was recorded at the end of treatment, at 72 h. The basal third of the cochlea lacked OHCs. Apoptosis occupied the adjacent 1/3, and the apical third contained preserved OHCs. 3-NT immunolabeling was extensive in OHCs and the SV. Gpx1 and Sod1 gene expression was downregulated. Gpx1 immunostaining diminished in middle and basal SV. More OHCs survived cisplatin than kanamycin towards the apex, despite undetectable evoked activity. Differential regulation of antioxidant enzyme levels suggests differences in the antioxidant response for both drugs.

Synthesis and Characterization of Reproducible Linseed Oil-Loaded Silica Nanoparticles with Potential Use as Oxygen Scavengers in Active Packaging.

Commercially available oxygen scavengers used to prevent lipid autoxidation, microbial growth and enzymatic browning in food products present several issues, which include the usage of metals and their moisture dependence to work properly. We present the synthesis and characterization of a moisture-independent oil-based oxygen scavenging system comprised of linseed oil and silica nanoparticles. The system was synthesized via sol-gel chemistry and was characterized using morphological analysis (SEM, AFM, TEM, and N2 adsorption/desorption), oil-loading analysis (TGA), and surface analysis (ζ-potential and ATR-FTIR). Performance of the system was evaluated through headspace measurements and reproducibility of synthetic procedure was verified using six replicates. Nanoparticles showed the desired spherical shape with a diameter of (122.7 ± 42.7 nm) and mesoporosity (pore diameter = 3.66 ± 0.08 nm), with an encapsulation efficiency of 33.9 ± 1.5% and a highly negative ζ-potential (-56.1 ± 1.2 mV) in basic solution. Performance of the system showed a promising high value for oxygen absorption of 25.8 ± 4.5 mL O2/g of encapsulated oil (8.3 ± 1.5 mL O2/g of nanocapsules) through a moisture independent mechanism, which suggests that the synthesized system can be used as an oxygen scavenger in dry atmosphere conditions.

Age-Related Inflammation and Oxidative Stress in the Cochlea Are Exacerbated by Long-Term, Short-Duration Noise Stimulation.

We have previously reported that young adult rats exposed to daily, short-duration noise for extended time periods, develop accelerated presbycusis starting at 6 months of age. Auditory aging is associated with progressive hearing loss, cell deterioration, dysregulation of the antioxidant defense system, and chronic inflammation, among others. To further characterize cellular and molecular mechanisms at the crossroads between noise and age-related hearing loss (ARHL), 3-month-old rats were exposed to a noise-accelerated presbycusis (NAP) protocol and tested at 6 and 16 months of age, using auditory brainstem responses, Real-Time Reverse Transcription-Quantitative PCR (RT-qPCR) and immunocytochemistry. Chronic noise-exposure leading to permanent auditory threshold shifts in 6-month-old rats, resulted in impaired sodium/potassium activity, degenerative changes in the lateral wall and spiral ganglion, increased lipid peroxidation, and sustained cochlear inflammation with advancing age. Additionally, at 6 months, noise-exposed rats showed significant increases in the gene expression of antioxidant enzymes (superoxide dismutase 1/2, glutathione peroxidase 1, and catalase) and inflammation-associated molecules [ionized calcium binding adaptor molecule 1, interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha]. The levels of IL-1ß were upregulated in the spiral ganglion and spiral ligament, particularly in type IV fibrocytes; these cells showed decreased levels of connective tissue growth factor and increased levels of 4-hydroxynonenal. These data provide functional, structural and molecular evidence that age-noise interaction contributes to exacerbating presbycusis in young rats by leading to progressive dysfunction and early degeneration of cochlear cells and structures. These findings contribute to a better understanding of NAP etiopathogenesis, which is essential as it affects the life quality of young adults worldwide.