EVALUATION OF THE TRANSITION FROM INTRAVENOUS TO SUBCUTANEOUS VEDOLIZUMAB IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. / VALORACIÓN DE LA TRANSICIÓN DE VEDOLIZUMAB INTRAVENOSO A SUBCUTÁNEO EN PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL.

AIMS: The aim of the study is to evaluate the clinical and biochemical response of inflammatory bowel disease (IBD) patients treated with vedolizumab, 16 weeks after transitioning from intravenous (iv) to subcutaneous (sc). METHODS: An observational, prospective, single-center cohort study was performed. Patients with IBD and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. RESULTS: 43 patients were included, 12 of them (27.9%) chose to transition to sc formulation. All included patients remained in remission during follow-up. At week 16 (w16), no significant differences were found in terms of calprotectin levels in patients on iv treatment (mean 146.6 ± SD 45.9) vs sc (159.26 ± 53.9) (p 0.9). Vedolizumab serum levels at w16 were higher in the sc group (22364.3 ± 5141.6) vs. iv (11425.9 ± 1514.2) (p 0.009). At w16, 9 (75%) of the patients in the SC group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. 4 patients (12.9%) in the iv group and 2 (16.6%) in the sc group presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site. CONCLUSION: In our experience, vedolizumab sc is a convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation.

Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat.

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.

Beneficios de la estandarización en el manejo de la apendicitis aguda / Benefits of standardization in the management of acute appendicitis

bjetivos. La apendicitis aguda (AA) es la patología quirúrgica pediátrica urgente más frecuente, pero su manejo postoperatorio es variable. La aplicación de protocolos minimiza esta variabilidad. Presentamos los resultados tras la optimización del protocolo de manejo en nuestro centro con objetivo de determinar su efectividad en cuanto a número de complicaciones infecciosas y optimización de recursos en nuestro medio. Material y métodos. Se realiza un estudio observacional retrospectivo en pacientes intervenidos de AA entre enero 2018 y agosto 2022. Comparamos dos cohortes, antes (1) y después del protocolo (2), subdividiéndolas según gravedad para un análisis por subgrupos: flemonosas (F), gangrenosas (G) y perforadas (P). Resultados. Incluimos 771 pacientes (1: 390/ 2: 381), con distribución homogénea, con mediana de edad 9,3 ± 2,8 años. La solicitud de analíticas previo al alta disminuyó de forma significativa (F: 3,9% vs. 0,5%; p= 0,026; G: 97,6% vs. 13,4%, p< 0,001). Los días de estancia hospitalaria se redujeron en los subgrupos F (1,2 IQR 0,7 vs. 1 IQR 0,36; p< 0,001), y G (4 IQR 1 vs. 3 IQR 1 días; p< 0,001). No se observaron diferencias en el número de abscesos entre los grupos (41 vs. 43 p= 0,73); sí en el subgrupo G (9 vs. 2; p= 0,029). Observamos una reducción del gasto de recursos en F y G. Conclusiones. En nuestro estudio, el subgrupo más beneficiado tras la optimización del protocolo fue el de las apendicitis gangrenosas con una reducción significativa en el número de complicaciones y en la utilización de recursos hospitalarios.(AU)

Objective. Acute appendicitis (AA) is the most frequent urgent surgical pathology in the pediatric population, but postoperative management is variable, with protocols minimizing variability. We present our results following the optimization of the management protocol in ourinstitution in order to establish its efficacy in terms of number of infectious complications and optimization of resources in our environment. Materials and methods. An observational, retrospective study of patients undergoing AA surgery from January 2018 to August 2022 was carried out. Two cohorts were compared, both before (1) and after (2) the implementation of the new protocol. They were divided according to severity in order to conduct a subgroup-based analysis –phlegmonous (PH), gangrenous (G), and perforated (P) appendicitis. Results. 771 patients (1: 390; 2: 381) were included, with a homogeneous distribution and a median age of 9.3 ± 2.8 years. Blood tests requested prior to discharge experienced a significant reduction (PH: 3.9% vs. 0.5%; p= 0.026; G: 97.6% vs. 13.4%, p< 0.001). Days of hospital stay decreased in the PH (1.2 IQR: 0.7 vs. 1 IQR: 0.36; p< 0.001) and G (4 IQR: 1 vs. 3 IQR: 1 days; p< 0.001) subgroups. No differences in the number of abscesses were found between groups (41 vs. 43; p= 0.73), but they were noted within subgroup G (9 vs. 2; p= 0.029). A reduction in resource expenses was detected in PH and G appendicitis. Conclusions. In our study, the most widely benefited subgroup following protocol optimization was the gangrenous appendicitis subgroup, with a significant reduction in the number of complications and the use of hospital resources.(AU)

Benefits of standardization in the management of acute appendicitis. / Beneficios de la estandarización en el manejo de la apendicitis aguda.

OBJECTIVE: Acute appendicitis (AA) is the most frequent urgent surgical pathology in the pediatric population, but postoperative management is variable, with protocols minimizing variability. We present our results following the optimization of the management protocol in our institution in order to establish its efficacy in terms of number of infectious complications and optimization of resources in our environment. MATERIALS AND METHODS: An observational, retrospective study of patients undergoing AA surgery from January 2018 to August 2022 was carried out. Two cohorts were compared, both before (1) and after (2) the implementation of the new protocol. They were divided according to severity in order to conduct a subgroup-based analysis -phlegmonous (PH), gangrenous (G), and perforated (P) appendicitis. RESULTS: 771 patients (1: 390; 2: 381) were included, with a homogeneous distribution and a median age of 9.3 ± 2.8 years. Blood tests requested prior to discharge experienced a significant reduction (PH: 3.9% vs. 0.5%; p= 0.026; G: 97.6% vs. 13.4%, p< 0.001). Days of hospital stay decreased in the PH (1.2 IQR: 0.7 vs. 1 IQR: 0.36; p< 0.001) and G (4 IQR: 1 vs. 3 IQR: 1 days; p< 0.001) subgroups. No differences in the number of abscesses were found between groups (41 vs. 43; p= 0.73), but they were noted within subgroup G (9 vs. 2; p= 0.029). A reduction in resource expenses was detected in PH and G appendicitis. CONCLUSIONS: In our study, the most widely benefited subgroup following protocol optimization was the gangrenous appendicitis subgroup, with a significant reduction in the number of complications and the use of hospital resources.

OBJETIVOS: La apendicitis aguda (AA) es la patología quirúrgica pediátrica urgente más frecuente, pero su manejo postoperatorio es variable. La aplicación de protocolos minimiza esta variabilidad. Presentamos los resultados tras la optimización del protocolo de manejo en nuestro centro con objetivo de determinar su efectividad en cuanto a número de complicaciones infecciosas y optimización de recursos en nuestro medio. MATERIAL Y METODOS: Se realiza un estudio observacional retrospectivo en pacientes intervenidos de AA entre enero 2018 y agosto 2022. Comparamos dos cohortes, antes (1) y después del protocolo (2), subdividiéndolas según gravedad para un análisis por subgrupos: flemonosas (F), gangrenosas (G) y perforadas (P). RESULTADOS: Incluimos 771 pacientes (1: 390/ 2: 381), con distribución homogénea, con mediana de edad 9,3 ± 2,8 años. La solicitud de analíticas previo al alta disminuyó de forma significativa (F: 3,9% vs. 0,5%; p= 0,026; G: 97,6% vs. 13,4%, p< 0,001). Los días de estancia hospitalaria se redujeron en los subgrupos F (1,2 IQR 0,7 vs. 1 IQR 0,36; p< 0,001), y G (4 IQR 1 vs. 3 IQR 1 días; p< 0,001). No se observaron diferencias en el número de abscesos entre los grupos (41 vs. 43 p= 0,73); sí en el subgrupo G (9 vs. 2; p= 0,029). Observamos una reducción del gasto de recursos en F y G. CONCLUSIONES: En nuestro estudio, el subgrupo más beneficiado tras la optimización del protocolo fue el de las apendicitis gangrenosas con una reducción significativa en el número de complicaciones y en la utilización de recursos hospitalarios.

Classification of light Yorkshire pigs at different production stages using ordinary least squares and machine learning methods.

Pig homogeneity and growth are major concerns for the pig industry today. Variability in pigs' size has a strong impact on profitability as uniformity plays a key role in the overall economic value of pigs produced. This research focused on statistical methods to identify pigs at risk of growth retardation at different stages of production. Data from 125 083 Yorkshire pigs at weaning (18-28 d), 59 533 pigs at the end of the nursery period (70-82 d) and 48 862 pigs at slaughter (155-170 d) were analyzed under three different cut-points (lowest 10, 20 and 30%) to characterize light animals. Records were randomly split into 2:1 training:testing sets, and each training data set was analyzed through an ordinary least squares approach and four machine learning algorithms (decision tree, random forest, and two alternative boosting approaches). A wide range of weighting functions were applied to give increased relevance to lighter pigs. Each resulting classification norm was used to classify light pigs in the testing data set. Both sensitivity and specificity were retained to construct the receiver operating characteristic curve, and the statistical performance of each analytical approach was evaluated by the area under the curve (AUC). In all production stages and cut-points, the random forest machine learning algorithm provided the highest AUC, closely followed by boosting procedures. For weaning BW (WW), factors related to birth BW and litter size accounted for more than 75% of the important prediction factors for light pigs. BW at the end of the nursery period and slaughter BW analyses revealed a similar pattern where WW and BW at the end of the nursery period accounted for more than 40 and 50% of statistical importance among the prediction factors, respectively. Machine learning algorithms are useful tools to easily evaluate the risk factors affecting the efficiency and homogeneity in swine. Since the BW at birth and weaning are key factors, sow nutrition and feeding management during gestation and lactation, along with piglet management during lactation, are identified as important influences on pig weight variability.

Can double J stent complications be reduced in pediatric patients? / ¿Podemos reducir las complicaciones de doble J en el paciente pediátrico?

OBJECTIVE: The use of double J (DJ) stents is frequent in urological pediatrics, but it is not exempt from morbidity. The objective of this study was to describe the risk factors (RF) of DJ complications in pediatric patients, and to analyze the quality of the information provided to the families with respect to the stent. MATERIALS AND METHODS: A retrospective study of patients undergoing surgery with DJ placement in the urology department from 2017 to 2022 was carried out. Study patients were divided into two groups -complicated (C) and non-complicated (NC). A multivariate analysis was performed to identify complication-related RFs, and a quality analysis as perceived by the families was conducted by means of a satisfaction survey (0 = total dissatisfaction; 10 = maximum satisfaction). RESULTS: 180 patients were included (236 DJs). The main diagnoses included renal transplantation (29.8%), ureteropelvic stenosis (26%), and urolithiasis (20.7%). Complication rate was 21.9%, with a mean comprehensive complication index (CCI) of 26.8. Prophylactic antibiotic therapy was not associated with fewer complications (97.3% vs. 98.1%; p= 0.727). Complication RFs included more than one stent (p< 0.001; OR= 6.628) and bilateral placement (p< 0.05; OR= 4.871). Poor registration in the medical records was associated with greater complications (p= 0.025). In the information quality survey, 20% reported a score lower than 7/10. CONCLUSIONS: DJ-associated morbidity has a direct relationship with DJ duration, bilaterality, and carrying more than one stent in a lifetime. Adequate registration in the medical records is associated with shorter DJ duration, and therefore, fewer complications. Antibiotic prophylaxis did not reduce complications, which means its routine use should be reconsidered.

OBJETIVOS: El uso de catéteres doble J (DJ) es un proceso frecuente en uropediatría, pero no exento de morbilidad. El objetivo de nuestro estudio es describir factores de riesgo (FR) de complicación de los DJ en pacientes pediátricos y comprobar la calidad de la información transmitida a las familias en relación al catéter. MATERIAL Y METODOS: Estudio retrospectivo de pacientes intervenidos en urología con colocación de DJ (2017­2022). Grupos a estudio: complicados (CC) y no complicados (SC). Realizamos un análisis multivariante para identificar FR relacionados con complicaciones y un análisis de calidad percibida por las familias mediante encuesta de satisfacción (0 no satisfacción, 10 máxima satisfacción). RESULTADOS: Incluimos 180 pacientes, (236 DJ). Diagnósticos principales: trasplante renal 29,8%, estenosis pieloureteral 26%, y urolitiasis 20,7%. La tasa de complicaciones fue del 21,9%, con un Comprehensive Complication Index (CCI) medio de 26,8. La antibioterapia profiláctica no se relaciona con menos complicaciones (97,3% vs 98,1% p= 0,727). FR de complicación: acumular más de un catéter (p< 0,001, OR 6,628) o la colocación bilateral (p< 0,05; OR 4,871). Un mal registro en la historia clínica se relacionó con más complicaciones (p= 0,025). En la encuesta de calidad de información recibida, el 20% reflejaron una puntuación inferior a 7/10. CONCLUSIONES: La morbilidad asociada al DJ se relaciona con su duración, la bilateralidad o acumular más de un catéter. Su adecuado registro en la historia clínica se relaciona con menor duración del mismo y, por tanto, menos complicaciones. La profilaxis antibiótica no ha demostrado disminuir las complicaciones, su uso rutinario debe ser revalorado.

¿Podemos reducir las complicaciones de doble J en el paciente pediátrico? / Can double J stent complications be reduced in pediatric patients?

Objetivos: El uso de catéteres doble J (DJ) es un proceso frecuenteen uropediatría, pero no exento de morbilidad. El objetivo de nuestroestudio es describir factores de riesgo (FR) de complicación de losDJ en pacientes pediátricos y comprobar la calidad de la informacióntransmitida a las familias en relación al catéter. Material y métodos: Estudio retrospectivo de pacientes intervenidos en urología con colocación de DJ (2017–2022). Grupos a estudio: complicados (CC) y no complicados (SC). Realizamos un análisismultivariante para identificar FR relacionados con complicaciones yun análisis de calidad percibida por las familias mediante encuesta desatisfacción (0 no satisfacción, 10 máxima satisfacción).Resultados. Incluimos 180 pacientes, (236 DJ). Diagnósticos principales: trasplante renal 29,8%, estenosis pieloureteral 26%, y urolitiasis20,7%. La tasa de complicaciones fue del 21,9%, con un ComprehensiveComplication Index (CCI) medio de 26,8. La antibioterapia profilácticano se relaciona con menos complicaciones (97,3% vs 98,1% p= 0,727). FR de complicación: acumular más de un catéter (p< 0,001, OR 6,628)o la colocación bilateral (p< 0,05; OR 4,871). Un mal registro en lahistoria clínica se relacionó con más complicaciones (p= 0,025). Enla encuesta de calidad de información recibida, el 20% reflejaron unapuntuación inferior a 7/10. Conclusiones: La morbilidad asociada al DJ se relaciona con suduración, la bilateralidad o acumular más de un catéter. Su adecuadoregistro en la historia clínica se relaciona con menor duración del mismo y, por tanto, menos complicaciones. La profilaxis antibiótica no hademostrado disminuir las complicaciones, su uso rutinario debe serrevalorado.(AU)

Objective: The use of double J (DJ) stents is frequent in urologicalpediatrics, but it is not exempt from morbidity. The objective of this studywas to describe the risk factors (RF) of DJ complications in pediatricpatients, and to analyze the quality of the information provided to thefamilies with respect to the stent.Materials and methods: A retrospective study of patients undergoing surgery with DJ placement in the urology department from 2017to 2022 was carried out. Study patients were divided into two groups –complicated (C) and non-complicated (NC). A multivariate analysis wasperformed to identify complication-related RFs, and a quality analysisas perceived by the families was conducted by means of a satisfactionsurvey (0 = total dissatisfaction; 10 = maximum satisfaction). Results: 180 patients were included (236 DJs). The main diagnosesincluded renal transplantation (29.8%), ureteropelvic stenosis (26%), andurolithiasis (20.7%). Complication rate was 21.9%, with a mean comprehensive complication index (CCI) of 26.8. Prophylactic antibiotic therapywas not associated with fewer complications (97.3% vs. 98.1%; p=0.727). Complication RFs included more than one stent (p<0.001; OR=6.628)and bilateral placement (p<0.05; OR=4.871). Poor registration in themedical records was associated with greater complications (p=0.025). Inthe information quality survey, 20% reported a score lower than 7/10.Conclusions: DJ-associated morbidity has a direct relationshipwith DJ duration, bilaterality, and carrying more than one stent in alifetime. Adequate registration in the medical records is associatedwith shorter DJ duration, and therefore, fewer complications. Antibiotic prophylaxis did not reduce complications, which means its routineuse should be reconsidered.(AU)

Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.

AIMS: Atrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies is hampered by the absence of scalable experimental human models that reflect AF-associated electrical remodelling. Therefore, we aimed to assess if AF-associated remodelling of cellular electrophysiology can be simulated in human atrial-like cardiomyocytes derived from induced pluripotent stem cells in the presence of retinoic acid (iPSC-aCM), and atrial-engineered human myocardium (aEHM) under short term (24 h) and chronic (7 days) tachypacing (TP). METHODS AND RESULTS: First, 24-h electrical pacing at 3 Hz was used to investigate whether AF-associated remodelling in iPSC-aCM and aEHM would ensue. Compared to controls (24 h, 1 Hz pacing) TP-stimulated iPSC-aCM presented classical hallmarks of AF-associated remodelling: (i) decreased L-type Ca2+ current (ICa,L) and (ii) impaired activation of acetylcholine-activated inward-rectifier K+ current (IK,ACh). This resulted in action potential shortening and an absent response to the M-receptor agonist carbachol in both iPSC-aCM and aEHM subjected to TP. Accordingly, mRNA expression of the channel-subunit Kir3.4 was reduced. Selective IK,ACh blockade with tertiapin reduced basal inward-rectifier K+ current only in iPSC-aCM subjected to TP, thereby unmasking an agonist-independent constitutively active IK,ACh. To allow for long-term TP, we developed iPSC-aCM and aEHM expressing the light-gated ion-channel f-Chrimson. The same hallmarks of AF-associated remodelling were observed after optical-TP. In addition, continuous TP (7 days) led to (i) increased amplitude of inward-rectifier K+ current (IK1), (ii) hyperpolarization of the resting membrane potential, (iii) increased action potential-amplitude and upstroke velocity as well as (iv) reversibly impaired contractile function in aEHM. CONCLUSIONS: Classical hallmarks of AF-associated remodelling were mimicked through TP of iPSC-aCM and aEHM. The use of the ultrafast f-Chrimson depolarizing ion channel allowed us to model the time-dependence of AF-associated remodelling in vitro for the first time. The observation of electrical remodelling with associated reversible contractile dysfunction offers a novel platform for human-centric discovery of antiarrhythmic therapies.

Global taxonomic, functional, and phylogenetic diversity of bees in apple orchards.

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes. Our findings reveal significant taxonomic dissimilarity among biogeographical zones. Interestingly, despite this dissimilarity, species from different zones share similar higher-level phylogenetic groups and similar ecological and behavioural traits (i.e. functional traits), likely due to habitat filtering caused by perennial monoculture systems managed intensively for crop production. Honey bee species dominated orchard communities, while other managed/manageable and wild species were collected in lower numbers. Moreover, the presence of herbaceous, uncultivated open areas and organic management practices were associated with increased wild bee diversity. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic diversity, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures.

Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies.

Introduction: Idiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication. Method: This is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aß2GP1). Results: Among the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aß2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37-1.71], p = 1 and RR: 0.7 [95% CI: 0.33-1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.

Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder specifically targeting pancreatic islet beta cells. Despite many efforts focused on identifying new therapies able to counteract this autoimmune attack and/or stimulate beta cells regeneration, TD1M remains without effective clinical treatments providing no clear advantages over the conventional treatment with insulin. We previously postulated that both the inflammatory and immune responses and beta cell survival/regeneration must be simultaneously targeted to blunt the progression of disease. Umbilical cord-derived mesenchymal stromal cells (UC-MSC) exhibit anti-inflammatory, trophic, immunomodulatory and regenerative properties and have shown some beneficial yet controversial effects in clinical trials for T1DM. In order to clarify conflicting results, we herein dissected the cellular and molecular events derived from UC-MSC intraperitoneal administration (i.p.) in the RIP-B7.1 mouse model of experimental autoimmune diabetes. Intraperitoneal (i.p.) transplantation of heterologous mouse UC-MSC delayed the onset of diabetes in RIP-B7.1 mice. Importantly, UC-MSC i. p. transplantation led to a strong peritoneal recruitment of myeloid-derived suppressor cells (MDSC) followed by multiple T-, B- and myeloid cells immunosuppressive responses in peritoneal fluid cells, spleen, pancreatic lymph nodes and the pancreas, which displayed significantly reduced insulitis and pancreatic infiltration of T and B Cells and pro-inflammatory macrophages. Altogether, these results suggest that UC-MSC i. p. transplantation can block or delay the development of hyperglycemia through suppression of inflammation and the immune attack.

A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Ananas ananassoides (Baker) L.B.Sm. a bromeliad from the savanna: seed morpho-anatomy and histochemistry.

Ananas ananassoides (Baker) L.B.Sm. is a wild pineapple, commonly found in the savannas. This study aimed to describe the morpho-anatomy and histochemistry of its seed. The observations were made in the longitudinal and transverse sections, using an optical microscope. The cell arrangement in the seed coat, ripples in the integument, the ratio of embryo size and endosperm amount, and the number of strata in the aleurone layer are anatomical characteristics that may contribute to distinguishing this species. The starch in the endosperm, lipids and proteins in the embryo, constitute the seed's main nutritional reserves. The homogeneous embryo and phenolic compounds present in the seed coat and in the aleurone layer possibly contribute to the dormancy in this species. This study presents information relevant to the taxonomy and physiology of A. ananassoides, which represents contributions to the global knowledge of this species with a high potential as ornamental.

Preliminary survey of the occurrence of mycotoxins in cereals and estimated exposure in a northwestern region of Mexico.

Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B1 (AFB1), ochratoxin A (OTA), and fumonisin (FB1) in paddy rice, polished rice, and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB1 in 21.21% of paddy rice samples and 11.11% of market maize samples. OTA was present in only 3.03% (one sample) of paddy rice samples. FB1 was detected in 87.50% and 88.88% of maize samples from field and market, respectively. The estimated human exposure was calculated for FB1 using the probable daily intake (PDI), which suggested that FB1 could contribute to the development of diseases through the consumption of contaminated maize. Positive samples indicated that some rice and maize samples were not suitable for human consumption. Further efforts are needed to continue monitoring mycotoxins and update national legislation on mycotoxins accordingly.

A reply to "Relevant factors in the eutrophication of the Uruguay River and the Río Negro".

A recent paper by Beretta-Blanco and Carrasco-Letelier (2021) claims that agricultural eutrophication is not one of the main causes for cyanobacterial blooms in rivers and artificial reservoirs. By combining rivers of markedly different hydrological characteristics e.g., presence/absence and number of dams, river discharge and geological setting, the study speculates about the role of nutrients for modulating phytoplankton chlorophyll-a. Here, we identified serious flaws, from erratic and inaccurate data manipulation. The study did not define how erroneous original dataset values were treated, how the variables below the detection/quantification limit were numerically introduced, lack of mandatory variables for river studies such as flow and rainfall, arbitrary removal of pH > 7.5 values (which were not outliers), and finally how extreme values of other environmental variables were included. In addition, we identified conceptual and procedural mistakes such as biased construction/evaluation of model prediction capability. The study trained the model using pooled data from a short restricted lotic section of the (large) Uruguay River and from both lotic and reservoir domains of the Negro River, but then tested predictability within the (small) Cuareim River. Besides these methodological considerations, the article shows misinterpretations of the statistical correlation of cause and effect neglecting basic limnological knowledge of the ecology of harmful algal blooms (HABs) and international research on land use effects on freshwater quality. The argument that pH is a predictor variable for HABs neglects overwhelming basic paradigms of carbon fluxes and change in pH because of primary productivity. As a result, the article introduces the notion that HABs formation are not related to agricultural land use and water residence time and generate a great risk for the management of surface waterbodies. This reply also emphasizes the need for good practices of open data management, especially for public databases in view of external reproducibility.

Experimental and Theoretical Studies of α-Linolenic Acid as Green Corrosion Inhibitor for Carbon Steel in 0.5 M Sulfuric Acid.

A component of Salvia hispanica, α-linolenic acid, has been evaluated as a green corrosion inhibitor for 1018 carbon steel in 0.5 M sulfuric acid using weight loss tests, potentiodynamic polarization curves and electrochemical impedance spectroscopy (EIS) measurements. Theoretical calculations using Density Functional Theory (DFT) were used also. The results have shown that this compound is a good corrosion inhibitor, with an efficiency which increased with an increase in its concentration up to 600 ppm, but it decreased with a further increase in the concentration. α-linolenic acid formed protective corrosion products layer because it was chemically adsorbed onto the steel surface according to a Langmuir type of adsorption isotherms. Polarization curves have shown that α-linolenic acid is a good, mixed type of inhibitor with a predominant effect on the cathodic hydrogen evolution reactions. EIS measurements indicated a charge transfer-controlled corrosion process. DFT calculations indicated that α-linolenic acid was more efficient in an acidic environment than in a neutral one because has a high tendency to donate electrons and can be easily protonated. In addition to this, it had the highest EHUMO value, the best chemical reactivity, the greatest tendency to transfer electrons and a greater facility of modifying its electronic configuration in the presence of carbon steel specimens according to its chemical hardness value.

Assessment of three commercial ELISAs for the detection of antibodies against Porcine epidemic diarrhea virus at different stages of the immune response.

Three commercial ELISAs -two based on spike (E1 and E3) and one on nucleocapsid protein (E2)-were used to analyze the development and persistence of antibodies against Porcine epidemic diarrhea virus (PEDV). Seventy-five four-week-old PEDV-negative piglets were inoculated orally with a European G1b PEDV (INOC) and fourteen were kept as controls (CTRL). After the inoculation, E3 detected positive animals as soon as 7 days post inoculation (dpi), while the earliest detection with E1 and E2 was at 14 dpi. All samples were positive at 21 and 28 dpi using E1 and E3, respectively, while E2 failed to detect 23.3 % of the inoculated pigs at any time point. The percentages of positive samples were different through the study: E1 and E3 > E2 from 14 to 56 dpi; and E3 > E1 > E2 from 56 to 154 dpi (P < 0.05). Five months after the inoculation, E3 still detected 92.0 % (IC95 % = 85.1-98.8 %) of pigs as positive, while E1 and E2 detected only 27.0 % (IC95 % = 16.0-37.9 %) and 0%, respectively. The sensitivity for E2 never exceeded 0.62. Specificity was 1 for all ELISAs. These different outcomes could be related to the ELISA strategies (indirect versus competition), the antigens used, the cut-off, or to other intrinsic factors of each test. The observed differences could be of importance when assessing whether older animals, such as fatteners or gilts, had previously been in contact with PEDV.

The occurrence of non-anatomical therapeutic chemical-international nonproprietary name molecules in suspected illegal or illegally traded health products in Europe: A retrospective and prospective study.

The General European Official Medicines Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the Quality of Medicines & HealthCare (EDQM), regularly organises market surveillance studies on specific categories of suspected illegal or illegally traded products. These studies are generally based on a combination of retrospective and prospective data collection over a defined period of time. This paper reports the results of the most recent study in this context with the focus on health products containing non-Anatomical Therapeutic Chemical-International Nonproprietary Name (ATC-INN) molecules. In total 1104 cases were reported by 16 countries for the period between January 2017 and the end of September 2019. The vast majority of these samples (83%) were collected from the illegal market, while only 3% originated from a legal source. For the rest of the samples, categorisation was not possible. Moreover, 69% of all the reported samples were presented as medicines, including sexual performance enhancers, sports performance enhancers, physical performance enhancers and cognitive enhancers or nootropic molecules that act on the central nervous system (CNS). Although the popularity of anabolics, PDE-5 inhibitors and CNS drugs in illegal products has already been reported, the study showed some new trends and challenges. Indeed, 11% of the samples contained molecules of biological origin, that is, research peptides, representing the second most reported category in this study. Furthermore, the study also clearly shows the increasing popularity of Selective Androgen Receptor Modulators and nootropics, two categories that need attention and should be further monitored.

[Discussion groups as an approach to assess knowledge, attitudes and practices of hand hygiene among the adult intensive care unit professionals from a referral hospital]. / Grupos de discusión como abordaje para valorar conocimiento, actitudes y prácticas de higiene de manos en profesionales de la unidad de cuidados intensivos de adultos de un hospital de referencia.

OBJECTIVES: The adherence to hand hygiene practices among the adult Intensive Care Unit (ICU) professionals in this hospital has not improved substantially in the last years, regardless of the theoretical training sessions conducted. A study was made of the knowledge, attitudes, and practices of the ICU personnel in this field. METHODS: Several small discussion groups with ICU staff organised by preventive medicine professionals were scheduled in March 2018. Semi-structured questions on hand hygiene and use of gloves were included. The points discussed were listed into strengths and weaknesses. Knowledge was then assessed using an anonymous questionnaire, after the sessions. RESULTS: Thirteen 60-minute sessions were carried out with 157 participants from all professional categories (82% from ICU, median=11 participants / session). The majority perceived hand hygiene as a priority issue of personal responsibility for patient safety. They identified factors that limit their ability to improve their adherence. Certain habits have more to do with personal preferences than with theoretical knowledge or technical indications. CONCLUSIONS: The discussion groups have helped to make a diagnosis of the situation that will be useful to strengthen those areas of improvement that have been identified. If we aim for a cultural change, and eliminate incorrect habits, it seems more useful to carry out adequate continuing education as part of the daily routine of professionals.