Anthraquinone-Modified Silica Nanoparticles as Heterogeneous Photocatalyst for the Oxidative Hydroxylation of Arylboronic Acids.

In this work, the synthesis and characterization of a heterogeneous photocatalyst based on spherical silica nanoparticles superficially modified with anthraquinone 2-carboxylic acid (AQ-COOH) are presented. The nanomaterial was characterized by TEM, SEM, FT-IR, diffuse reflectance, fluorescence, NMR, DLS, XRD and XPS. These analyses confirm the covalent linking of AQ-COOH with the NH2 functionality in the nanomaterial and, more importantly, the photocatalyst retains its photophysical properties once bound. The heterogeneous photocatalyst was successfully employed in the aerobic hydroxylation of arylboronic acids to phenols under sustainable reaction conditions. Phenols were obtained in high yields (up to 100 %) with low catalyst loading (3.5 mol %), reaching TOF values of 3.7 h-1 . Using 2-propanol as solvent at room temperature, the visible light photocatalysis produced H2 O2 as a key intermediate to promote the aerobic hydroxylation of arylboronic acids. The heterogeneous photocatalyst was reused at least 5 times, without modification of the nanomaterial structure and morphology. This simple heterogeneous system showed great catalytic activity under sustainable reaction conditions.

Somatic and germline ATM variants in non-small-cell lung cancer: Therapeutic implications.

ATM is an apical kinase of the DNA damage response involved in the repair of DNA double-strand breaks. Germline ATM variants (gATM) have been associated with an increased risk of developing lung adenocarcinoma (LUAD), and approximately 9% of LUAD tumors harbor somatic ATM mutations (sATM). Biallelic carriers of pathogenic gATM exhibit a plethora of immunological abnormalities, but few studies have evaluated the contribution of immune dysfunction to lung cancer susceptibility. Indeed, little is known about the clinicopathological characteristics of lung cancer patients with sATM or gATM alterations. The introduction of targeted therapies and immunotherapies, and the increasing number of clinical trials evaluating treatment combinations, warrants a careful reexamination of the benefits and harms that different therapeutic approaches have had in lung cancer patients with sATM or gATM. This review will discuss the role of ATM in the pathogenesis of lung cancer, highlighting potential therapeutic approaches to manage ATM-deficient lung cancers.

Left Bundle Branch Area Pacing Versus Biventricular Pacing as Initial Strategy for Cardiac Resynchronization.

BACKGROUND: Left bundle branch area pacing (LBBAP) for cardiac resynchronization therapy (CRT) is an alternative to biventricular pacing (BiVp). OBJECTIVES: The purpose of this study was to compare the outcomes between LBBAP and BiVp as an initial implant strategy for CRT. METHODS: In this prospective multicenter, observational, nonrandomized study, first-time CRT implant recipients with LBBAP or BiVp were included. The primary efficacy outcome was a composite of heart failure (HF)-related hospitalization and all-cause mortality. The primary safety outcomes were acute and long-term complications. Secondary outcomes included postprocedural New York Heart Association functional class and electrocardiographic and echocardiographic parameters. RESULTS: A total of 371 patients (median follow-up of 340 days [IQR: 206-477 days]) were included. The primary efficacy outcome occurred in 24.2% in the LBBAP vs 42.4% in the BiVp (HR: 0.621 [95% CI: 0.415-0.93]; P = 0.021) group, driven by a reduction in HF-related hospitalizations (22.6% vs 39.5%; HR: 0.607 [95% CI: 0.397-0.927]; P = 0.021) without significant difference in all-cause mortality (5.5% vs 11.9%; P = 0.19) or differences in long-term complications (LBBAP: 9.4% vs BiVp: 15.2%; P = 0.146). LBBAP resulted in shorter procedural (95 minutes [IQR: 65-120 minutes] vs 129 minutes [IQR: 103-162 minutes]; P < 0.001) and fluoroscopy times (12 minutes [IQR: 7.4-21.1 minutes] vs 21.7 minutes [IQR: 14.3-30 minutes]; P < 0.001), shorter QRS duration (123.7 ± 18 milliseconds vs 149.3 ± 29.1 milliseconds; P < 0.001), and higher postprocedural left ventricular ejection fraction (34.1% ± 12.5% vs 31.4% ± 10.8%; P = 0.041). CONCLUSIONS: LBBAP as an initial CRT strategy resulted in a lower risk of HF-related hospitalizations compared to BiVp. A reduction in procedural and fluoroscopy times, shorter paced QRS duration, and improvements in left ventricular ejection fraction compared with BiVp were observed.

Quantitative determination of voriconazole by thionine reduction and its potential application in a pharmaceutical and clinical setting.

Voriconazole (VCZ) is a triazolic drug used to treat serious fungal infections and invasive mycosis and has also been more recently used as a generic antifungal treatment. However, VCZ therapies can cause undesirable side effects and doses must be carefully monitored before administration to avoid or reduce severe toxic effects. Analytical techniques used to quantify VCZ are mostly based on HPLC/UV and often associated with multiple technical steps as well as expensive equipment. The present work aimed to develop an accessible and affordable spectrophotometric technique in the visible range (λ = 514 nm) for the simple quantification of VCZ. The technique was based on VCZ-induced reduction of thionine (TH, red) to leucothionine (LTH, colorless) under alkaline conditions. The reaction showed a linear correlation over the range of 1.00 µg mL-1 to 60.00 µg mL-1 at room temperature, the limits of detection and quantification being 1.93 µg mL-1 and 6.45 µg mL-1, respectively. VCZ degradation products (DPs) according to 1H and 13C-NMR spectrometric determinations not only showed good agreement with the ones previously reported (DP1 and DP2 - T. M. Barbosa, G. A. Morris, M. Nilsson, R. Rittner and C. F. Tormena, RSC Adv., 2017, DOI: 10.1039/c7ra03822d), but also revealed a new degradation product (DP3). Mass spectrometry not only confirmed the presence of LTH as a result of the VCZ DP-induced TH reduction, but also revealed the formation of a novel and stable Schiff base as a reaction product between DP1 and LTH. The latter finding became significant as it stabilizes the reaction for quantification purposes, by hindering LTH ↔TH redox reversibility. This analytical method was then validated according to the ICH Q2 (R1) guidelines, and additionally, it could be demonstrated as applicable for the reliable VCZ quantification in commercially available tablets. Importantly, it also represents a useful tool for detecting toxic threshold concentrations in human plasma from VCZ-treated patients, alerting when these risky limits are exceeded. In this way, this technique independent from sophisticated equipment, highly qualifies as a low-cost, reproducible, trustable, and non-laborious alternative method for VCZ measurements from different matrices.

Prevalence of zoonotic and non-zoonotic Rickettsia in horses: A systematic review and meta-analysis.

In a broad sense, Rickettsiae are a group of microorganisms that can be transmitted mechanically or biologically to animals and humans. Rickettsioses are associated with hematic manifestations. Its prevalence in humans, dogs and other animals has been widely explored, but not in equine species. To determine the prevalence of Rickettsia infection in horses. A systematic review of the literature was carried out in five databases for the proportion of horses infected with Rickettsia, defined by molecular and immunological techniques. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence and 95% confidence intervals (CI). The Cochran's Q test and the I2 statistic were used to assess the between-study-heterogeneity. The pooled prevalence of Rickettsia in equines was 37.0% (95% CI: 26.0%-47.0%), with significant heterogeneity among studies (I2 = 98.12%). In the subgroup analysis, the prevalence of Rickettsia in horses was found to be 24.0% (95%CI: 10.0%-41.0%) for IFI, 47.0% (95%CI: 30.0%-64.0%) for IFA, 14.0% (95%CI: 11.0%-17.0%) for IFAT and 39.0% (95%CI: 0.0%-95.0%) for PCR. There was a high prevalence of Rickettsia among horses, with some of the species being zoonotic, with their corresponding implications for humans, which increasingly are in close contact with equines, particularly horses and their ticks, posing a risk for spillover and transmission.

Re-irradiation in patients with progressive or recurrent brain metastases from extracranial solid tumors: A novel prognostic index.

BACKGROUND: Most studies evaluating factors associated with the survival of patients with brain metastases (BM) have focused on patients with newly diagnosed BM. This study aimed to identify prognostic factors associated with survival after brain re-irradiation in order to develop a new prognostic index. METHODS: This 5-year retrospective study included patients treated with repeat-radiotherapy for recurrent BM at the "Instituto Nacional de Cancerología" of Mexico between 2015 and 2019. Significant variables in the multivariate Cox regression analysis were used to create the brain re-irradiation index (BRI). Survival and group comparisons were performed using the Kaplan-Meier method and the log-rank test. RESULTS: Fifty-seven patients receiving brain re-irradiation were identified. Most patients were women (75.4%) with a mean age at BM diagnosis of 51.4 years. Lung and breast cancer were the most prevalent neoplasms (43.9% each). Independent prognostic factors for shorter survival after re-irradiation were: Age >50 years (hazard ratio [HR]:2.5 [95% confidence interval [CI], 1.1-5.8]; p = 0.026), uncontrolled primary tumor (HR:5.5 [95% CI, 2.2-13.5]; p < 0.001), lesion size >20 mm (4.6 [95% CI, 1.7-12.2]; p = 0.002), and an interval <12 months between radiation treatments (HR:4.3 [95% CI, 1.7-10.6]; p = 0.001). Median survival (MS) after re-irradiation was 14.6 months (95% CI, 8.2-20.9).MS of patients stratified according to the BRI score was 17.38, 10.34, and 2.82 months, with significant differences between all groups. CONCLUSIONS: The new BRI can be easily implemented for the prognostic classification of cancer patients with progressive or recurrent BM from extracranial solid tumors.

Targeted Therapies and Utility of the Lung-molGPA in Non-Small-Cell Lung Cancer Patients with Brain Metastases.

INTRODUCTION: Therapeutic advances have increased the survival of non-small-cell lung cancer (NSCLC) patients as well as the lifetime risk of being diagnosed with brain metastases (BM). Although BM have historically been associated with poor prognosis, it is unclear whether they remain a strong predictor of reduced survival. This study aimed to evaluate the prognostic value of BM and the utility of the Lung-molGPA. METHODS: This single-center retrospective database analysis included 1,393 NSCLC patients with newly diagnosed BM who registered at the Instituto Nacional de Cancerología of Mexico (INCan) from 2010 to 2020. The Kaplan-Meier method and log-rank test were used for the survival analysis. Survival times were calculated from the date of NSCLC diagnosis (OS), or BM diagnosis, to the date of death or last follow-up. Cox proportional-hazards models were used to calculate the hazard ratio (HR) for death and the significance of the parameters evaluated. RESULTS: Out of 1,058 patients who underwent genetic testing for epidermal growth factor receptor (EGFR) mutations and/or anaplastic lymphoma kinase (ALK) rearrangements, 650 had a positive tumor mutational/rearrangement status (543 had EGFR mutations, 104 had ALK rearrangements, and 3 had both EGFR and ALK alterations). Median OS did not differ between patients with BM and without BM (17.7 months [95% CI, 15.4-19.0] vs. 16.6 months [95% CI, 14.3-19.0]; p = 0.362). In contrast, the presence of BM was associated with worse OS in patients with a negative tumor mutational status (HR: 1.225 [95% CI, 1.041-1.443]; p = 0.015), who did not receive TKI therapy (HR: 1.269 [95% CI, 1.082-1.488]; p = 0.003), or with non-adenocarcinoma histology (HR: 1.582 [95% CI, 1.118-2.238]; p = 0.01). The median survival after BM diagnosis was 4.27, 6.96, 14.68, and 18.89 months for adenocarcinoma patients with Lung-molGPA scores 0-1, 1.5-2, 2.5-3, and 3.5-4, respectively (p < 0.0001). For non-adenocarcinoma patients with Lung-molGPA scores 0-1, 1.5-2, and 2.5-3, the corresponding estimates were 0.95, 2.89, and 9.39 months, respectively (p < 0.0001). CONCLUSIONS: These results show that the prognosis of NSCLC patients with BM is no longer uniformly poor and should be individually assessed. Furthermore, the validity of the Lung-molGPA was confirmed in an independent population from a different geographical region.

Nuclear DNA Fragmentation in Boar Spermatozoa: Measurement Methods and Reproductive Performance Implications.

The aim of this research was to compare the different techniques to measure sperm nuclear DNA fragmentation (sDF) and to check its relations to boar reproductive value, classical spermiogram parameters, and reproductive results of the doses in sows. Sperm chromatin stability assay (SCSA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and sperm chromatin dispersion test (SCD, Halomax®) results were compared, finding a statistically significant correlation only between SCSA and TUNEL results. The fertility direct boar effect (DBE) index, calculated from the whole productive life of the boar, was not correlated (p > 0.05) with sDF (measured by any technique). Total or progressive sperm motility was not correlated with sDF, while it found a positive correlation between TUNEL measure and abnormal acrosomes (%) and between SCD measure and total sperm morphological abnormalities (%). No significant correlations were obtained between fertility or prolificacy results and sDF results with the different techniques. However, in the case of total born and SCSA measure, the correlation was close to significance (r partial = -0.095; p = 0.066), appointing to a tendency; as SCSA increases, the number of total piglets born decreases. In conclusion, although the different techniques for the sDF seem not to target exactly the same DNA events and the relationship between their values and the reproductive results and the classical spermiogram results is still to be elucidated, the studied sDF techniques may offer extra information that could be useful for the management of AI studs.

Prevertebral cervical approach to posterior mediastinum parathyroid adenomas.

BACKGROUND: About 4 years ago, we described the pure endoscopic cervical approach to posterior mediastinum parathyroid adenomas, which we called the "prevertebral cervical approach". At that time, we had operated on three patients and did not have enough quality videos to demonstrate this approach. After broadening our experience, we present our results and show this technique through a video. METHODS: From June 2015 to January 2021, information on patients undergoing the prevertebral cervical approach was obtained from a specific prospective database, including clinical presentation, biochemistry, preoperative imaging, surgical approach and patient outcomes. The step by step technique is described for both right- and left-sided adenomas, by means of a short video clip. RESULTS: Ten patients were operated on using this technique. Seven adenomas were right-sided and three were left-sided. The mean surgical time was 33 ± 7 min. There were neither intraoperative nor major postoperative complications. Seven patients presented with a slight subcutaneous emphysema, which did not cause complaints. All patients were discharged the day after surgery, except for one patient with a previous open neck removal of four glands due to secondary hyperparathyroidism, which required calcium replacement. Calcium and parathyroid hormone levels were normalised in the other nine patients after surgery. One patient experienced a transient recurrent laryngeal nerve injury which was spontaneously resolved within 1 month. No permanent recurrent laryngeal nerve injury was found. The postoperative cosmetic outcomes were excellent. CONCLUSION: In our experience, the pure cervical endoscopic approach has shown a high feasibility and short operation time, with excellent postoperative results regarding patient comfort, length of stay and disease cure. This approach also offers a very reasonable procedure cost, and may result in a less aggressive surgical option when compared with thoracic approaches.

The Effects of Vitamin C on the Multiple Pathophysiological Stages of COVID-19.

Currently available anti-viral drugs may be useful in reducing the viral load but are not providing the necessary physiological effects to reduce the SARS-CoV-2 complications efficiently. Treatments that provide better clinical outcomes are urgently needed. Vitamin C (ascorbic acid, AA) is an essential nutrient with many biological roles that have been proven to play an important part in immune function; it serves as an antioxidant, an anti-viral, and exerts anti-thrombotic effects among many other physiological benefits. Research has proven that AA at pharmacological doses can be beneficial to patients with acute respiratory distress syndrome (ARDS) and other respiratory illnesses, including sepsis. In addition, High-Dose Intravenous Vitamin C (HDIVC) has proven to be effective in patients with different viral diseases, such as influenza, chikungunya, Zika, and dengue. Moreover, HDIVC has been demonstrated to be very safe. Regarding COVID-19, vitamin C can suppress the cytokine storm, reduce thrombotic complications, and diminish alveolar and vascular damage, among other benefits. Due to these reasons, the use of HDIVC should be seriously considered in complicated COVID-19 patients. In this article, we will emphasize vitamin C's multiple roles in the most prominent pathophysiological processes presented by the COVID-19 disease.

Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves' disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial.

BACKGROUND: Currently, both the American Thyroid Association and the European Thyroid Association recommend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves' Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to provide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidectomy for GD. METHODS: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery.Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoperative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. CONCLUSIONS: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this setting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03980132.

Physical activity: academic stress regulator in time of covid-19 pandemic. Covid-19 and academic stress / Actividad física: regulador de estrés académico en tiempos de pandemia Covid-19. Covid-19 y estrés académico

Introduction: The pandemic derived from the presence of the SARS-CoV-2 virus, forced the population to adopt measures for biosecurity purposes, such as: healthy distance and confinement, the tasks that were normally carried out outside the home were temporarily stopped, triggering with this a series of stressors. Objective: The objective of this work was to analyze the relationship between physical activity and perceived academic stress during the SARS-CoV-2 pandemic in students of the Faculty of Medicine and Surgery of the Universidad Regional del Sureste. Methods: It was a descriptive-cross-sectional study, the sample was determined conveniently since the surveys were applied to second- and third-year students, through the Moodle platform of the advisor of this project, surveying 6 groups, the Cognitivist Systemic Inventory was applied to study academic stress (SISCO) and the International Physical Activity Questionnaire (IPAQ). Results: 84% refer to physical activity on a daily basis, in addition to the fact that 65.4% of students consider themselves to be under moderate stress, 16.6% do not present stress, 15.5% with mild stress and only 2.5% with severe stress, this perhaps derived from individual personalities and levels of self-demand. Conclusions: The main stressors are related to the self-directed study and the characteristics of the complementary activities of self-directed learning. The manifestations of stress are varied and of multifactorial origin, the most common being chronic fatigue, anxiety and headache. The practice of regular physical activity is related to greater physical and psycho-emotional well-being.(AU)

Introducción: La pandemia derivada de la presencia del virus SARS-CoV-2, obligó a la población a adoptar medidas con fines de bioseguridad, tales como: distancia sana y confinamiento, las tareas que normalmente se realizaban fuera del hogar fueron detenidas temporalmente, desencadenando con esto una serie de factores estresantes. Objetivo: El objetivo de este trabajo fue analizar la relación entre la actividad física y el estrés académico percibido durante la pandemia SARS-CoV-2 en estudiantes de la Facultad de Medicina y Cirugía de la Universidad Regional del Sureste. Métodos: Se trató de un estudio descriptivo-transversal, la muestra se determinó convenientemente ya que las encuestas se aplicaron a estudiantes de segundo y tercer año, a través de la plataforma Moodle del asesor de este proyecto, encuestando a 6 grupos, para el estudio del estrés académico se aplicó el Inventario Cognitivista Sistémico (SISCO) y el Cuestionario Internacional de Actividad Física (IPAQ). Resultados: el 84% refiere realizar actividad física en el día a día, además de que el 65,4% de los estudiantes se considera bajo estrés moderado, el 16,6% no presenta estrés, el 15,5% con estrés leve y solo el 2,5% con estrés severo, esto quizás derivado de personalidades individuales y niveles de autoexigencia. Conclusiones: Los principales factores estresantes están relacionados con el estudio autodirigido y las características de las actividades complementarias del aprendizaje autodirigido. Las manifestaciones del estrés son variadas y de origen multifactorial, siendo las más frecuentes: fatiga crónica, ansiedad y dolor de cabeza. La práctica de actividad física regular está relacionada con un mayor bienestar físico y psicoemocional.(AU)

Impact of detecting plasma EGFR mutations with ultrasensitive liquid biopsy in outcomes of NSCLC patients treated with first- or second-generation EGFR-TKIs.

BACKGROUND: Few trials have evaluated the utility of liquid biopsies to detect epidermal growth factor receptor mutations (EGFRm) at the time of response evaluation and its association with the clinical characteristics and outcomes of non-small-cell lung cancer (NSCLC) patients. OBJECTIVE: This study aimed to evaluate, in a real-world clinical setting, the prevalence of plasma EGFRm and its association with the clinical characteristics, response and survival outcomes of NSCLC patients under treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This observational study enrolled advanced or metastatic NSCLC patients, with confirmed tumor EGFRm, receiving treatment with first- or second-generation EGFR-TKIs. Blood samples for the detection of plasma EGFRm were collected at the time of response evaluation and processed using the Target Selector™ assay. The main outcomes were the detection rate of plasma EGFRm, median Progression-Free Survival (PFS) and Overall Survival (OS) according to plasma EGFR mutational status. RESULTS: Of 84 patients, 50 (59.5%) had an EGFRm detected in plasma. After a median follow-up of 21.1 months, 63 patients (75%) had disease progression. The detection rate of plasma EGFRm was significantly higher in patients with disease progression than in patients with partial response or stable disease (68.3% versus 33.3%; P< 0.01). PFS and OS were significantly longer in patients without plasma EGFRm than among patients with plasma EGFRm (14.3 months [95% CI, 9.25-19.39] vs 11.0 months [95% CI, 8.61-13.46]; P= 0.034) and (67.8 months [95% CI, 39.80-95.94] vs 32.0 months [95% CI, 17.12-46.93]; P= 0.006), respectively. A positive finding in LB was associated with the presence of ⩾ 3 more metastatic sites (P= 0.028), elevated serum carcinoembryonic (CEA) at disease progression (P= 0.015), and an increase in CEA with respect to baseline levels (P= 0.038). CONCLUSIONS: In NSCLC patients receiving EGFR-TKIs, the detection of plasma EGFRm at the time of tumor response evaluation is associated with poor clinical outcomes.

Carbon Nanotori Structures for Thermal Transport Applications on Lubricants.

Carbon nanostructures have been recently applied to improve industrial manufacturing processes and other materials; such is the case for lubricants used in the metal-mechanic industry. Nanotori are toroidal carbon nanostructures, obtained from chemical treatment of multi-wall carbon nanotubes (MWCNTs). This material has been shown to have superb anti-wear and friction reduction performance, having the ability to homogeneously disperse within water in concentrations between 1-2 wt.%. Obtained results of these novel nanostructures under water mixtures and novel additives were a set point to our studies in different industrial lubricants. In the present work, nanotori structures have been applied in various filler fractions as reinforcement to evaluate the behavior in thermal transport of water-based (WB) and oil-based (OB) lubricants. Temperature-dependent experiments to evaluate the thermal conductivity were performed using a thermal water bath ranging from room temperature up to 323 K. The obtained results showed a highly effective and favorable improvement in the heat transport of both lubricants; oil-based results were better than water-based results, with nanotori structures increasing the lubricants' thermal transport properties by 70%, compared to pure lubricant.

Seasonal Changes of Nuclear DNA Fragmentation in Boar Spermatozoa in Spain.

There are numerous cases when conventional spermiogram parameters are all within an acceptable range but boar subfertility persists. The total sperm nuclear DNA fragmentation index (tDFI) is a trait related to fertility and prolificacy problems that is not routinely evaluated in commercial AI boars. The aim of this research was to study the effect of the photoperiod, season and reproductive age of the boar on tDFI (measured by SCSA) of 1279 ejaculates from 372 different boars belonging to 6 different breeds located in 6 AI studs in Spain. tDFI data ranged from 0.018% to 20.1%. Although there was a significant single boar effect in the tDFI occurrence, a negative correlation between the tDFI and the age of the boar was found (p < 0.001). tDFI would decrease due to aging of the boar 0.66% each year old within the observed age range. After including age as a covariate in the ANCOVA, no differences were found in tDFI between photoperiods when the sperm collection date was evaluated. However, when the date of the production of semen in the testis was evaluated, the total percentage of spermatozoa with fragmented nuclear DNA was 1.46% higher in the increasing photoperiod in comparison to the decreasing photoperiod (p < 0.0001). On the other hand, for both dates, the lowest tDFI values corresponded to minimum day length for decreasing photoperiod phase (autumn), while the highest tDFI values were found in summer (maximum day length for decreasing photoperiod phase).

Tratamiento farmacológico de la litiasis renal / Medical treatment of renal stones

INTRODUCCIÓN: La prevalencia de la patología litiásica se estima en un 5% al 15%, con una clara tendencia al aumento en los países industrializados. Los pacientes con episodios recurrentes de litiasis renal presentan un riesgo aumentado de enfermedad renal crónica que puede potencialmente limitar su expectativa de vida. OBJETIVO: Revisión y síntesis de las opciones terapéuticas recomendadas para la prevención en la recurrencia de cálculos urinarios basadas en el tipo de cálculo o alteración urinaria en orina de 24 horas, según las guías clínicas y publicaciones recientes. CONCLUSIONES: Medidas dietéticas y farmacológicas han demostrado una reducción de hasta el 60% en la recurrencia de episodios clínicos cuando son dirigidas según el tipo de cálculo y los resultados de los estudios metabólicos. El aumento en la prevalencia mundial de esta patología y el potencial riesgo de enfermedad renal crónica en pacientes recurrentes, justifican la necesidad de ampliar los conocimientos fisiopatológicos que precipitan la formación de litiasis urinarias para el desarrollo de nuevos tratamientos más eficaces en la prevención de esta enfermedad

INTRODUCTION: Prevalence of urolitiasis is estimated between 5-15% with a clear trend to increasing in the industrialized countries. Stone recurrent patients show an increased risk of chronic renal disease which can potentially limit their life expectancy. OBJECTIVE: A review and summary of the different recommended treatment options to prevent urinary stone recurrence based on the type of calculi or urinary metabolic alterations in 24 h urine, according to recent guidelines and publications. CONCLUSIONS: Dietetic and pharmacologic measures, when addressed depending on the type of stone and results of metabolic evaluation have shown a decrease up to 60% of the recurrent clinical events. The increase of prevalence worldwide and the potential risk of chronic kidney disease in these patients clearly justify the need of increasing physiopathologic knowledge leading urolithiasis formation in order to develop new and more effective drugs for its prevention

Medical treatment of renal stones. / Tratamiento farmacológico de la litiasis renal.

INTRODUCTION: Prevalence of urolithiasisis estimated between 5-15% with a clear trend to increasing in the industrialized countries. Stone recurrent patients show an increased risk of chronic renal disease which can potentially limit their life expectancy. OBJECTIVE: A review and summary of the different recommended treatment options to prevent urinary stone recurrence based on the type of calculi or urinary metabolic alterations in 24 h urine, according to recent guidelines and publications. CONCLUSIONS: Dietetic and pharmacologic measures, when addressed depending on the type of stone and results of metabolic evaluation have shown a decrease up to 60% of the recurrent clinical events. The increase of prevalence worldwide and the potential risk of chronic kidney disease in these patients clearly justify the need of increasing physiopathologic knowledge leading urolithiasis formation in order to develop new and more effective drugs for its prevention.

INTRODUCCIÓN: La prevalencia de lapatología litiásica se estima en un 5% al 15%, con unaclara tendencia al aumento en los países industrializados. Los pacientes con episodios recurrentes de litiasis renal presentan un riesgo aumentado de enfermedad renal crónica que puede potencialmente limitar su expectativade vida.OBJETIVO: Revisión y síntesis de las opciones terapéuticas recomendadas para la prevención en la recurrencia de cálculos urinarios basadas en el tipo de cálculo o alteración urinaria en orina de 24 horas, según las guías clínicas y publicaciones recientes.CONCLUSIONES: Medidas dietéticas y farmacológicas han demostrado una reducción de hasta el 60% en la recurrencia de episodios clínicos cuando son dirigidas según el tipo de cálculo y los resultados de los estudios metabólicos. El aumento en la prevalencia mundial de esta patología y el potencial riesgo de enfermedad renal crónica en pacientes recurrentes, justifican la necesidad de ampliar los conocimientos fisiopatológicos que precipitan la formación de litiasis urinarias para el desarrollo de nuevos tratamientos más eficaces en la prevención de esta enfermedad.

Selective Tumor Cell Apoptosis and Tumor Regression in CDH17-Positive Colorectal Cancer Models using BI 905711, a Novel Liver-Sparing TRAILR2 Agonist.

Activation of TRAILR2 has emerged as an important therapeutic concept in cancer treatment. TRAILR2 agonistic molecules have only had limited clinical success, to date, due either to lack of efficacy or hepatotoxicity. BI 905711 is a novel tetravalent bispecific antibody targeting both TRAILR2 and CDH17 and represents a novel liver-sparing TRAILR2 agonist specifically designed to overcome the disadvantages of previous strategies. Here, we show that BI 905711 effectively triggered apoptosis in a broad panel of CDH17-positive colorectal cancer tumor cells in vitro. Efficient induction of apoptosis was dependent on the presence of CDH17, as exemplified by the greater than 1,000-fold drop in potency in CDH17-negative cells. BI 905711 demonstrated single-agent tumor regressions in CDH17-positive colorectal cancer xenografts, an effect that was further enhanced upon combination with irinotecan. Antitumor efficacy correlated with induction of caspase activation, as measured in both the tumor and plasma. Effective tumor growth inhibition was further demonstrated across a series of different colorectal cancer PDX models. BI 905711 induced apoptosis in both a cis (same cell) as well as trans (adjacent cell) fashion, translating into significant antitumor activity even in xenograft models with heterogeneous CDH17 expression. In summary, we demonstrate that BI 905711 has potent and selective antitumor activity in CDH17-positive colorectal cancer models both in vitro and in vivo. The high prevalence of over 95% CDH17-positive tumors in patients with colorectal cancer, the molecule preclinical efficacy together with its potential for a favorable safety profile, support the ongoing BI 905711 phase I trial in colorectal cancer and additional CDH17-positive cancer types (NCT04137289).