Redox proteomics in melanoma cells: An optimized protocol.

Cancer development and progression are intimately related with post-translational protein modifications, e.g., highly reactive thiol moiety of cysteines enables structural rearrangements resulting in redox biological switches. In this context, redox proteomics techniques, such as 2D redox DIGE, biotin switch assay and OxIcat are fundamental tools to identify and quantify redox-sensitive proteins and to understand redox mechanisms behind thiol modifications. Given the great variability in redox proteomics protocols, problems including decreased resolution of peptides and low protein amounts even after enrichment steps may occur. Considering the biological importance of thiol's oxidation in melanoma, we adapted the biotin-switch assay technique for melanoma cells in order to overcome the limitations and improve coverage of detected proteins.

Age-related patterns in high-risk alcohol and cannabis use and their associations with positive and negative affect in young adulthood.

OBJECTIVE: We examined age-varying associations between young adult simultaneous alcohol and marijuana/cannabis use (SAM) and heavy episodic drinking (HED) and positive and negative affect to inform harm reduction efforts. METHODS: Young adults reporting past-year alcohol use (n = 556; ages 19-25) were recruited in a state where alcohol and nonmedical cannabis use was legal for those 21 +. Participants provided 24 repeated monthly assessments. Among those reporting past-month cannabis use on at least one survey, logistic time-varying effect models estimated (1) the age-varying prevalence of and associations between past-month SAM and HED and (2) age-varying unique associations of affect with SAM and HED. RESULTS: There was a positive age-varying association between HED and SAM over time that was highest at age 19 (OR = 7.56), decreased until age 20.7 (OR = 3.39), increased until age 23.0 (OR = 4.85), and decreased until the association became non-significant by age 25. Negative affect was positively associated with SAM from ages 20.7 to 23.0, peaking at age 21.8 (OR = 1.36). Positive affect was positively associated with HED from ages 19.4 to 20.4 (peak OR = 1.25) and ages 22.5 to 24.5 (peak OR = 1.38). In contrast, positive affect was not uniquely associated with SAM nor negative affect with HED across ages 19-25. CONCLUSIONS: While HED and SAM were positively associated throughout young adulthood and interventions could target them in tandem, their associations with affect suggest differential etiologic processes. Preventive intervention and harm reduction efforts should attend to psychological context in which these behaviors occur.

Cortical inhibition on TMS-EEG: interstimulus interval effect on short-interval paired-pulse.

In mental disorders, paired-pulse (PP) transcranial magnetic stimulation and electroencephalography (TMS-EEG) recordings usage is increasing to directly evaluate the cortical inhibition of motor and nonmotor regions. One of the most common measures to assess the inhibition is the short-interval cortical inhibition (SICI), which depends on the interstimulus interval (ISI). This measure has been widely used in the motor cortex. However, the number of studies that evaluate other nonmotor regions, such as the dorsolateral prefrontal cortex (DLPFC), are increasing and there is still little knowledge on how the ISI affects those areas.In this pilot study, six subjects underwent a SICI protocol over the DLPFC using ISI values of 2 and 4ms with the aim of comparing them. TMS-EEG signals for both ISIs were characterized regarding the amplitude and latency of the TMS-evoked potentials (TEP) P60 and N100. Whereas the variation of cortical inhibition between ISIs is almost significant for N100, with higher inhibition for an ISI of 2ms, for TEP P60 the variation was not appreciable. Findings are in accordance with the ones in the state-of-the-art obtained in the motor cortex and suggest that a greater inhibition is likely to be produced with an ISI of 2ms.Clinical relevance- This pilot study indicates that cortical inhibition might be better assessed when DLPFC is stimulated with an ISI of 2ms in the SICI protocol.

Tracking the sources of Leptospira and nutrient flows in two urban watersheds of Puerto Rico.

This study investigated the relationship between nutrient levels, source of fecal contamination, and pathogenic Leptospira in Puerto Rico's northern coast and San Juan Bay Estuary (SJBE) aquatic ecosystems. Microbial source tracking (MST) was also used to investigate the connections between sources of feces contamination and the presence of Leptospira. Eighty-seven water samples were collected during the June (n=44) and August (n=43) in 2020. To quantify phosphorus and nitrogen concentrations, standard USEPA protocols were utilized, specifically Methods 365.4 for total and dissolved phosphorus, 351.2 for total Kjeldahl nitrogen and ammonium, and 353.2 for nitrate. Lipl32 gene-specific quantitative polymerase chain reaction (qPCR) was used to detect the presence of Leptospira. Human (HF183), canine (BacCan-UCD), and equine (HoF597) MST assays were utilized to trace the origins of fecal contamination. Forty one percent of the locations exceeded Puerto Rico's authorized total phosphorus limit of 160 g L-1, while 34% exceeded the total nitrogen limit of 1700 g L-1. Nearly half of the streams examined are affected by eutrophication. The MST analysis identified human and canine feces as the most prevalent contaminants, affecting approximately 50% of the sites. In addition, Leptospira was detected in 32% of the June samples. There was a significant correlation (r = 0.79) between the incidence of pathogenic Leptospira and the human bacterial marker (HF183). This study illuminates the central role of anthropogenic inputs in nutrient enrichment and pathogen proliferation in Puerto Rico's aquatic ecosystems.

[Impact of the ''Enhanced Recovery After Surgery'' program in knee arthroplasty at the institutional level]. / Impacto del programa ''Enhanced Recovery After Surgery'' en artroplastía de rodilla a nivel institucional.

INTRODUCTION: total knee arthroplasty has gained popularity over decreasing pain, restoring mobility and improving patients' quality of life. At the institutional level, there is no multidisciplinary model in the treatment of our patients, and in our environment, physical rehabilitation starts late, making it difficult for patients to reincorporate and attain adequate pain control. MATERIAL AND METHODS: a controlled, randomized, prospective and longitudinal study was conducted, 55 patients underwent total knee arthroplasty, assigned to two study groups: the ERAS (enhanced recovery after surgery) group (n = 27) and the usual group (n = 28). Inclusion criteria were patients with Kellgren-Lawrence classification grade 4 gonarthrosis, age between 30-70 years and follow-up for six months. Descriptive statistics were performed using medians and interquartile range, while inferential statistics were performed using the Kruskal-Wallis test. RESULTS: the results obtained at six months showed no statistically significant differences in age (p = 0.327) and gender (p = 0.588). The results obtained in the scales of VAS, WOMAC and IKDC showed statistically significant difference (p = 0.000). The rapid recovery group with a 120° flexion median and the usual group with 90° flexion, both groups with 0° extension. CONCLUSIONS: the enhanced recovery after surgery pathway in joint replacement procedures showed good results on pain, function, mobility and complications compared to patients undergoing usual management.

INTRODUCCIÓN: la artroplastía total de rodilla ha ganado popularidad sobre la disminución del dolor, restablecer la movilidad y mejorar la calidad de vida de los pacientes. A nivel institucional, no existe un modelo multidisciplinario en el tratamiento de nuestros pacientes y en nuestro medio la rehabilitación física se inicia de manera tardía, dificultando la reincorporación de los pacientes y el control analgésico. MATERIAL Y MÉTODOS: se realizó un estudio clínico controlado, aleatorizado, prospectivo y longitudinal que incluyó 55 pacientes sometidos a artroplastía de rodilla, asignados a dos grupos de estudio: el grupo ERAS (Enhanced Recovery After Surgery) (n = 27) y el grupo habitual (n = 28). Los criterios de inclusión fueron pacientes con gonartrosis grado IV de Kellgren y Lawrence, edad comprendida entre 30-70 años y seguimiento de seis meses. La estadística descriptiva se realizó mediante medianas y rango intercuartílico, mientras la estadística inferencial mediante la prueba de Kruskal-Wallis. RESULTADOS: los resultados obtenidos a los seis meses no mostraron diferencias estadísticas significativas de edad (p = 0.327) y género (p = 0.588). Los resultados obtenidos en las escalas de EVA, WOMAC e IKDC mostraron diferencia estadística significativa (p = 0.000). El grupo de recuperación rápida con una mediana de flexión de 120° y el grupo habitual con flexión de 90°, ambos grupos con extensión de 0°. CONCLUSIONES: el programa de recuperación rápida en procedimientos de remplazo articular, mostró buenos resultados sobre el dolor, función, movilidad y complicaciones en comparación con los pacientes sometidos al manejo habitual.

Comparability of the Retinomax K-plus 3 handheld autorefractometer in quick mode versus on-table autorefractometer in standard mode.

INTRODUCTION: This study analyzes the comparability of measurements taken by a Retinomax K-plus 3 handheld autorefractometer in Quick mode and a Topcon KR-800 on-table autorefractometer in standard mode on the pediatric population, and establishes their correlation. METHODS: It is a retrospective comparative study. Spherical diopter power (SPH), cylindrical diopter power (CYL), angle of cylindrical axis (AX), and spherical equivalent (SE) were measured with the Retinomax in Quick mode and with the Topcon in standard mode. Each patient was evaluated in cycloplegic and non-cycloplegic conditions by both autorefractometers. Student's t-test was performed between the two instruments for SPH, CYL, and SE. The Pearson correlation coefficient was calculated and the dispersion was represented using Bland-Altman graphs, also evaluating the subgroup of patients under 4 years of age. A descriptive analysis of the percentages of measures that differed was performed. RESULTS: It included 98 eyes of 49 subjects (age range: 3-16 years). The data for HPS without cycloplegia are virtually identical, whereas with cycloplegia there is a hyperopic bias of +0.5 diopters measured with Retinomax. CYL results are very similar with and without cycloplegia. There is a high Pearson correlation for both instruments (>0.91) and a low degree of dispersion in the Bland-Altman plots under cycloplegia. CONCLUSION: The Retinomax data were consistent with those obtained by Topcon. The Retinomax is a useful instrument for detecting refractive errors in children between 3 and 16 years of age.

Correlating Eucalyptus leaf metabolomics with preference of the bronze bug, Thaumastocoris peregrinus.

Eucalyptus species are among the most planted trees in forestry production, an ever-increasing commercial activity worldwide. Forestry expansion demands a continuous search for preventive and sanitary measures against pests and diseases. Massive application of phytosanitary products is incompatible with the forestry sector, so forest health management must be based on other principles. In this context, studies on insect plant relationships mediated by plant metabolites may contribute information relevant to plant resistance and genotype selection. In this study, we analyzed the leaf metabolome of four Eucalyptus species commonly planted in southern South America, to correlate this chemical information with feeding preference of Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae), an important pest of eucalypt plantations. Gas chromatography mass spectrometry analyses were performed on polar and non-polar leaf extracts from Eucalyptus globulus, Eucalyptus grandis, Eucalyptus robusta, and Eucalyptus tereticornis (Myrtaceae). Feeding preferences were assessed in two-choice laboratory bioassays resulting in a preference gradient of the four plant species. Moreover, a performance bioassay where we contrasted survival and development time between the most and least preferred plants, showed a clear correlation with preference both in survival and developmental time of the most susceptible nymph instar. We found that species with high or low feeding preferences differ significantly in several foliar metabolites, which may be acting as feeding stimulants or deterrents for T. peregrinus. These findings may provide useful criteria for choosing Eucalyptus genotypes when planting in bronze bug infested areas.

Cost-Effectiveness Analysis of 68Ga-DOTATATE PET/MRI in Radiotherapy Planning in Patients with Intermediate-Risk Meningioma.

BACKGROUND AND PURPOSE: While contrast-enhanced MR imaging is the criterion standard in meningioma diagnosis and treatment response assessment, gallium 68Ga-DOTATATE PET/MR imaging has increasingly demonstrated utility in meningioma diagnosis and management. Integrating 68Ga-DOTATATE PET/MR imaging in postsurgical radiation planning reduces the planning target volume and organ-at-risk dose. However, 68Ga-DOTATATE PET/MR imaging is not widely implemented in clinical practice due to higher perceived costs. Our study analyzes the cost-effectiveness of 68Ga-DOTATATE PET/MR imaging for postresection radiation therapy planning in patients with intermediate-risk meningioma. MATERIALS AND METHODS: We developed a decision-analytical model based on both recommended guidelines on meningioma management and our institutional experience. Markov models were implemented to estimate quality-adjusted life-years (QALY). Cost-effectiveness analyses with willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY were performed from a societal perspective. Sensitivity analyses were conducted to validate the results. Model input values were based on published literature. RESULTS: The cost-effectiveness results demonstrated that 68Ga-DOTATATE PET/MR imaging yields higher QALY (5.47 versus 5.05) at a higher cost ($404,260 versus $395,535) compared with MR imaging alone. The incremental cost-effectiveness ratio analysis determined that 68Ga-DOTATATE PET/MR imaging is cost-effective at a willingness to pay of $50,000/QALY and $100,000/QALY. Furthermore, sensitivity analyses showed that 68Ga-DOTATATE PET/MR imaging is cost-effective at $50,000/QALY ($100,000/QALY) for specificity and sensitivity values above 76% (58%) and 53% (44%), respectively. CONCLUSIONS: 68Ga-DOTATATE PET/MR imaging as an adjunct imaging technique is cost-effective in postoperative treatment planning in patients with meningiomas. Most important, the model results show that the sensitivity and specificity cost-effective thresholds of 68Ga-DOTATATE PET/MR imaging could be attained in clinical practice.

A novel estimate of biological aging by multiple fitness tests is associated with risk scores for age-related diseases.

Introduction: Recent research highlights the need for a correct instrument for monitoring the individual health status, especially in the elderly. Different definitions of biological aging have been proposed, with a consistent positive association of physical activity and physical fitness with decelerated aging trajectories. The six-minute walking test is considered the current gold standard for estimating the individual fitness status in the elderly. Methods: In this study, we investigated the possibility of overcoming the main limitations of assessing fitness status based on a single measure. As a result, we developed a novel measure of fitness status based on multiple fitness tests. In 176 Sardinian individuals aged 51-80 years we collected the results of eight fitness tests to measure participants' functional mobility, gait, aerobic condition, endurance, upper and lower limb strength, and static and dynamic balance. In addition, the participants' state of health was estimated through validated risk scores for cardiovascular diseases, diabetes, mortality, and a comorbidity index. Results: Six measures contributing to fitness age were extracted, with TUG showing the largest contribution (beta = 2.23 SDs), followed by handgrip strength (beta = -1.98 SDs) and 6MWT distance (beta = -1.11 SDs). Based on fitness age estimates, we developed a biological aging measure using an elastic net model regression as a linear combination of the results of the fitness tests described above. Our newly developed biomarker was significantly associated with risk scores for cardiovascular events (ACC-AHA: r = 0.61; p = 0.0006; MESA: r = 0.21; p = 0.002) and mortality (Levine mortality score: r = 0.90; p = 0.0002) and outperformed the previous definition of fitness status based on the six-minute walking test in predicting an individual health status. Discussion: Our results indicate that a composite measure of biological age based on multiple fitness tests may be helpful for screening and monitoring strategies in clinical practice. However, additional studies are needed to test standardisation and to calibrate and validate the present results.

Mars 2020 Perseverance Rover Studies of the Martian Atmosphere Over Jezero From Pressure Measurements.

The pressure sensors on Mars rover Perseverance measure the pressure field in the Jezero crater on regular hourly basis starting in sol 15 after landing. The present study extends up to sol 460 encompassing the range of solar longitudes from L s  âˆ¼ 13°-241° (Martian Year (MY) 36). The data show the changing daily pressure cycle, the sol-to-sol seasonal evolution of the mean pressure field driven by the CO2 sublimation and deposition cycle at the poles, the characterization of up to six components of the atmospheric tides and their relationship to dust content in the atmosphere. They also show the presence of wave disturbances with periods 2-5 sols, exploring their baroclinic nature, short period oscillations (mainly at night-time) in the range 8-24 min that we interpret as internal gravity waves, transient pressure drops with duration ∼1-150 s produced by vortices, and rapid turbulent fluctuations. We also analyze the effects on pressure measurements produced by a regional dust storm over Jezero at L s  âˆ¼ 155°.

High-flow nasal oxygen vs. standard oxygen therapy for patients undergoing transcatheter aortic valve replacement with conscious sedation: a randomised controlled trial.

BACKGROUND: Minimally invasive surgery is becoming more common and transfemoral transcatheter aortic valve replacement is offered to older patients with multiple comorbidities. Sternotomy is not required but patients must lie flat and still for up to 2-3 h. This procedure is increasingly being performed under conscious sedation with supplementary oxygen, but hypoxia and agitation are commonly observed. METHODS: In this randomised controlled trial, we hypothesised that high-flow nasal oxygen would provide superior oxygenation as compared with our standard practice, 2 l min-1 oxygen by dry nasal specs. This was administered using the Optiflow THRIVE Nasal High Flow delivery system (Fisher and Paykel, Auckland, New Zealand) at a flow rate of 50 l min-1 and FiO2 0.3. The primary endpoint was the change in arterial partial pressure of oxygen (pO2) during the procedure. Secondary outcomes included the incidence of oxygen desaturation, airway interventions, the number of times the patient reached for the oxygen delivery device, incidence of cerebral desaturation, peri-operative oxygen therapy duration, hospital length of stay and patient satisfaction scores. RESULTS: A total of 72 patients were recruited. There was no difference in change in pO2 from baseline using high-flow compared with standard oxygen therapy: median [IQR] increase from 12.10 (10.05-15.22 [7.2-29.8]) to 13.69 (10.85-18.38 [8.5-32.3]) kPa vs. decrease from 15.45 (12.17-19.33 [9.2-22.8]) to 14.20 (11.80-19.40 [9.7-35.1]) kPa, respectively. The percentage change in pO2 after 30 min was also not significantly different between the two groups (p = 0.171). There was a lower incidence of oxygen desaturation in the high-flow group (p = 0.027). Patients in the high-flow group assigned a significantly higher comfort score to their treatment (p ≤ 0.001). CONCLUSION: This study has demonstrated that high flow, compared with standard oxygen therapy, does not improve arterial oxygenation over the course of the procedure. There are suggestions that it may improve the secondary outcomes studied. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 13,804,861. Registered on 15 April 2019. https://doi.org/10.1186/ISRCTN13804861.

The effect of prolonged and nocturnal use of contact lenses on the cornea: about a case of corneal decompensation and decreased endothelial count.

Corneal edema and decreased endothelial cell count are complications related to chronic low-grade hypoxia experienced by contact lens wearers, primarily due to prolonged and overnight wear. This case shows the example of a patient who has blurred vision problems in both eyes and who underwent a complete ophthalmologic examination that included photographs, corneal topography and endothelial cell count. Subsequently, the corneal metabolism, the etiopathogenesis and the complications derived from the use of contact lenses are reviewed.

[Translated article] Pilot study to determine the association between gut microbiota and fragility hip fracture.

INTRODUCTION: Hip fractures are the most common cause of hospital admission to orthopaedic departments in Europe and they generate a major health problem. Therefore, it is of great interest to identify additional risk factors that will help us to better understand the pathophysiology of these fractures and improve our preventive capacity. There is sufficient data to support the theory of modulation of bone mass by gut microbiota (osteomicrobiology); however, there is a lack of human clinical studies directly linking microbiota to hip fracture risk. MATERIAL AND METHODS: Observational, analytical, case-control study. The sample consisted of 50 patients and it was distributed as follows: 25 elderly patients with fragility hip fracture and 25 subjects without fracture. The intestinal microbiota was determined by DNA extraction from stool samples and 16S ribosomal DNA sequencing after generation of gene libraries. RESULTS: Alpha diversity revealed an elevation of the estimators for the taxonomic class level in the hip fracture group. The orders Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales and Enterobacterales were the dominant orders in both groups. In patients with fracture, a significant percentage increase in the orders Bacteroidales (p<.001) and Peptostreptococcales-Tissierellales (p<.005) was observed, as well as a decrease in the orders Lachnospirales (p<.001) compared to controls. CONCLUSIONS: This study has found an association between a specific microbiota in elderly patients with fragility hip fracture. These findings open the door to new strategies to prevent hip fractures. Modification of the microbiota through probiotics may prove to be an effective method to reduce the risk of hip fracture.

Impacto del programa "Enhanced Recovery After Surgery" en artroplastía de rodilla a nivel institucional / Impact of the "Enhanced Recovery After Surgery" program in knee arthroplasty at the institutional level

Resumen: Introducción: la artroplastía total de rodilla ha ganado popularidad sobre la disminución del dolor, restablecer la movilidad y mejorar la calidad de vida de los pacientes. A nivel institucional, no existe un modelo multidisciplinario en el tratamiento de nuestros pacientes y en nuestro medio la rehabilitación física se inicia de manera tardía, dificultando la reincorporación de los pacientes y el control analgésico. Material y métodos: se realizó un estudio clínico controlado, aleatorizado, prospectivo y longitudinal que incluyó 55 pacientes sometidos a artroplastía de rodilla, asignados a dos grupos de estudio: el grupo ERAS (Enhanced Recovery After Surgery) (n = 27) y el grupo habitual (n = 28). Los criterios de inclusión fueron pacientes con gonartrosis grado IV de Kellgren y Lawrence, edad comprendida entre 30-70 años y seguimiento de seis meses. La estadística descriptiva se realizó mediante medianas y rango intercuartílico, mientras la estadística inferencial mediante la prueba de Kruskal-Wallis. Resultados: los resultados obtenidos a los seis meses no mostraron diferencias estadísticas significativas de edad (p = 0.327) y género (p = 0.588). Los resultados obtenidos en las escalas de EVA, WOMAC e IKDC mostraron diferencia estadística significativa (p = 0.000). El grupo de recuperación rápida con una mediana de flexión de 120o y el grupo habitual con flexión de 90o, ambos grupos con extensión de 0o. Conclusiones: el programa de recuperación rápida en procedimientos de remplazo articular, mostró buenos resultados sobre el dolor, función, movilidad y complicaciones en comparación con los pacientes sometidos al manejo habitual.

Abstract: Introduction: total knee arthroplasty has gained popularity over decreasing pain, restoring mobility and improving patients' quality of life. At the institutional level, there is no multidisciplinary model in the treatment of our patients, and in our environment, physical rehabilitation starts late, making it difficult for patients to reincorporate and attain adequate pain control. Material and methods: a controlled, randomized, prospective and longitudinal study was conducted, 55 patients underwent total knee arthroplasty, assigned to two study groups: the ERAS (enhanced recovery after surgery) group (n = 27) and the usual group (n = 28). Inclusion criteria were patients with Kellgren-Lawrence classification grade 4 gonarthrosis, age between 30-70 years and follow-up for six months. Descriptive statistics were performed using medians and interquartile range, while inferential statistics were performed using the Kruskal-Wallis test. Results: the results obtained at six months showed no statistically significant differences in age (p = 0.327) and gender (p = 0.588). The results obtained in the scales of VAS, WOMAC and IKDC showed statistically significant difference (p = 0.000). The rapid recovery group with a 120o flexion median and the usual group with 90o flexion, both groups with 0o extension. Conclusions: the enhanced recovery after surgery pathway in joint replacement procedures showed good results on pain, function, mobility and complications compared to patients undergoing usual management.

Pilot study to determine the association between gut microbiota and fragility hip fracture. / Estudio piloto para determinar la asociación entre la microbiota intestinal y la fractura de cadera por fragilidad.

INTRODUCTION: Hip fractures are the most common cause of hospital admission to orthopaedic departments in Europe and they generate a major health problem. Therefore, it is of great interest to identify additional risk factors that will help us to better understand the pathophysiology of these fractures and improve our preventive capacity. There is sufficient data to support the theory of modulation of bone mass by gut microbiota (osteomicrobiology); however, there is a lack of human clinical studies directly linking microbiota to hip fracture risk. MATERIAL AND METHODS: Observational, analytical, case-control study. The sample consisted of 50 patients and it was distributed as follows: 25 elderly patients with fragility hip fracture and 25 subjects without fracture. The intestinal microbiota was determined by DNA extraction from stool samples and 16S ribosomal DNA sequencing after generation of gene libraries. RESULTS: Alpha diversity revealed an elevation of the estimators for the taxonomic class level in the hip fracture group. The orders Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales and Enterobacterales were the dominant orders in both groups. In patients with fracture, a significant percentage increase in the orders Bacteroidales (p<.001) and Peptostreptococcales-Tissierellales (p<.005) was observed, as well as a decrease in the orders Lachnospirales (p<.001) compared to controls. CONCLUSIONS: This study has found an association between a specific microbiota in elderly patients with fragility hip fracture. These findings open the door to new strategies to prevent hip fractures. Modification of the microbiota through probiotics may prove to be an effective method to reduce the risk of hip fracture.

Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery.

Improving echographic monitoring of hemodynamics in critically ill patients: Validation of right cardiac output measurements through the modified subcostal window.

OBJECTIVE: We aimed to assess the usefulness of using the right ventricle outflow tract (RVOT) velocity-time integral (VTI) for echocardiographic monitoring of cardiac output compared to the gold standard, the VTI along the left ventricle outflow tract (LVOT). DESIGN: Prospective observational study. SETTING: A tertiary intensive care unit. PATIENTS: 100 consecutive patients. INTERVENTIONS: echocardiographic monitoring in critically ill patients. MAIN VARIABLES OF INTEREST: We used intraclass correlation coefficients (ICC) to compare echocardiographic measurements of LVOT VTI through apical window with RVOT VTI through the parasternal and modified subcostal windows and to assess interobserver reproducibility. Preplanned post hoc analyses compared the ICC between ventilated and nonventilated patients. RESULTS: At the time of echocardiography, 44 (44%) patients were mechanically ventilated and 28 (28%) were receiving vasoactive drugs. Good-quality measurements were obtained through the parasternal short-axis and/or apical views in 81 (81%) patients and in 100 (100%) patients through the subcostal window. Consistency with LVOT VTI was moderate for RVOT VTI measured from the modified subcostal view (ICC 0.727; 95%CI: 0.62-0.808) and for RVOT VTI measured from the transthoracic view (0.715; 95%CI: 0.59-0.807). CONCLUSIONS: Measurements of RVOT VTI are moderately consistent with measurements of LVOT VTI. Adding the modified subcostal window allows monitoring RVOT VTI in all the patients of this selected cohort, even those under mechanical ventilation.

Does the meteorological origin of heat waves influence their impact on health? A 6-year morbidity and mortality study in Madrid (Spain).

BACKGROUND: In Spain, two synoptic-scale conditions influence heat wave formation. The first involves advection of warm and dry air masses carrying dust of Saharan origin (North African Dust (NAF) = 1). The second entails anticyclonic stagnation with high insolation and stability (NAF) = 0). Some studies show that the meteorological origin of these heat waves may affect their impact on morbidity and mortality. OBJECTIVE: To determine whether the impact of heat waves on health outcomes in Madrid (Spain) during 2013-2018 varied by synoptic-scale condition. METHODOLOGY: Outcome data consist of daily mortality and daily hospital emergency admissions (morbidity) for natural, circulatory, and respiratory causes. Predictors include daily maximum and minimum temperatures and daily mean concentrations of NO2, PM10, PM2.5, NO2, and O3. Analyses adjust for insolation, relative humidity, and wind speed. Generalized linear models were performed with Poisson link between the variables controlling for trend, seasonality, and auto-regression in the series. Relative Risks (RR) and Attributable Risks (AR) were determined. The RRs for mortality attributable to high temperatures were similar regardless of NAF status. For hospital admissions, however, the RRs for hot days with NAF = 0 are higher than for days with NAF = 1. We also found that atmospheric pollutants worsen morbidity and mortality, especially PM10 concentrations when NAF = 1 and O3 concentrations when NAF = 0. RESULTS: The effect of heat waves on morbidity and mortality depends on the synoptic situation. The impact is greater under anticyclonic stagnation conditions than under Saharan dust advection. Further, the health impact of pollutants such as PM10 and O3 varies according to the synoptic situation. CONCLUSIONS: Based on these findings, we strongly recommend prevention plans to include data on the meteorological situation originating the heat wave, on a synoptic-scale, as well as comprehensive preventive measures against the compounding effect of high temperatures and pollution.

Air pollution and meteorological variables' effects on COVID-19 first and second waves in Spain.

The aim of this research is to study the influence of atmospheric pollutants and meteorological variables on the incidence rate of COVID-19 and the rate of hospital admissions due to COVID-19 during the first and second waves in nine Spanish provinces. Numerous studies analyze the effect of environmental and pollution variables separately, but few that include them in the same analysis together, and even fewer that compare their effects between the first and second waves of the virus. This study was conducted in nine of 52 Spanish provinces, using generalized linear models with Poisson link between levels of PM10, NO2 and O3 (independent variables) and maximum temperature and absolute humidity and the rates of incidence and hospital admissions of COVID-19 (dependent variables), establishing a series of significant lags. Using the estimators obtained from the significant multivariate models, the relative risks associated with these variables were calculated for increases of 10 µg/m3 for pollutants, 1 °C for temperature and 1 g/m3 for humidity. The results suggest that NO2 has a greater association than the other air pollution variables and the meteorological variables. There was a greater association with O3 in the first wave and with NO2 in the second. Pollutants showed a homogeneous distribution across the country. We conclude that, compared to other air pollutants and meteorological variables, NO2 is a protagonist that may modulate the incidence and severity of COVID-19, though preventive public health measures such as masking and hand washing are still very important. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04190-z.