The role of coagulation factors VIII, IX and XI in the prediction and mediation of recurrent thrombotic events in children with non-central venous catheter deep vein thrombosis.

BACKGROUND: The role of elevated coagulation factors VIII (FVIII), FIX, FXI for the prediction of recurrent thrombotic events in children after an index non-central venous catheter (non-CVC) related deep vein thrombosis (DVT) remains unclear. OBJECTIVE: This study investigates the predictive role of FVIII, FIX, and FXI for recurrent thrombosis in children with index non-CVC DVTs, and the mediation effect of FVIII on chronic inflammation and recurrent thrombosis. METHODS: Children aged 0-18 years diagnosed with an index non-CVC related DVT (1993-2020) were included in this single-center retrospective cohort study. Plasma levels of FVIII, FIX, FXI were measured cross-sectionally ≥30 days after the acute DVT. The association between the continuous variables FVIII, FIX, FXI and thrombosis recurrence was investigated using uni- and multivariable logistic regression, adjusting for age, sex, and chronic inflammation. Mediation analysis assessed the role of FVIII as a mediator between chronic inflammation and recurrent thrombosis. Ethics approval was obtained. RESULTS: A total of 139 children with an index non-CVC related DVT were included. Thirty-eight (27 %) had a recurrent thrombosis at a median of 237 days (P25-P75 65-657 days) after the index DVT. In uni- and multivariable-analysis, FVIII, FIX or FXI did not predict thrombosis recurrence; However, chronic inflammation was an independent predictor. There was no evidence that FVIII mediated the effect of chronic inflammation on thrombosis recurrence. CONCLUSION: We found no evidence that elevated FVIII, FIX or FXI predicted thrombosis recurrence, or evidence of a mediating role of FVIII. Underlying chronic inflammation predicted venous recurrent thrombotic events in this cohort.

Effects of Genetic Origin of Honeybees and Climate on Prevalence and Infestation Levels of Varroa.

The objective of this study was to evaluate the effect of honeybee genetic origin, climate type and the interactions between these variables on the prevalence and infestation levels of Varroa in a large population of honeybee colonies (n = 1134). For each colony, the morphotype, haplotype and climate type were determined. No differences between the Africanized, European and Hybrid morphotypes were found for the prevalence and infestation levels of Varroa (p > 0.05). Differences between honeybee haplotypes were found for the prevalence of Varroa (p < 0.05), and the prevalence was higher in the African haplotype than in the European haplotype. No differences between honeybee haplotypes were found for the infestation levels of Varroa (p > 0.05). Differences were found between climate type for the prevalence and infestation levels of Varroa (p < 0.05): the temperate sub-humid climate had a higher prevalence and higher infestation levels than the semi-warm climate and the warm sub-humid climate. Correlations between the infestation levels of Varroa and mean annual temperature, mean annual precipitation, winter precipitation and Lang index were found.

Exercise-induced deep vein thrombosis in the subclavian vein in an elite female athlete.

An adolescent female presented to the emergency room with pain, swelling and a palpable lump in the right axilla following activity on a rowing ergometer. The differential diagnosis at the time of presentation was deep vein thrombosis, mass compression and cellulitis. An ultrasound scan revealed an occlusive thrombus of the right axillary and subclavian veins, basilic vein and proximal cephalic vein. The patient underwent pharmacomechanical thrombolysis followed by catheter-directed thrombolysis. Dynamic venogram testing revealed venous thoracic outlet syndrome (VTOS) and a transaxillary first rib resection was performed to decompress the costoclavicular space. Genetic testing revealed the patient was heterozygous for factor V Leiden. Two rounds of balloon dilatation plasty were performed to relieve recurring symptoms due to scarring and persisting compression, 1 and 3 years post rib resection. After extensive shared decision-making, the patient returned to sport, reporting only intermittent symptoms of post-thrombotic syndrome. This case sheds light on the importance of early diagnosis of VTOS for successful return to sport.

French Canadian cross-cultural adaptation of CAPTSure©, an index for the Clinical Assessment of Post-Thrombotic Syndrome in children.

PURPOSE: Post-thrombotic syndrome (PTS) is the most common complication of deep venous thrombosis (DVT). The index for the Clinical Assessment of Post-Thrombotic Syndrome in children (CAPTSure©) is a clinical tool for the diagnosis and severity rating of PTS in pediatric patients. The purpose of this study was to translate and adapt CAPTSure© for French-speaking patients. METHODS: We conducted a cross-sectional study to perform linguistic and cultural adaptation of CAPTSure©, using a rigorous translation process followed by cognitive debriefings in twenty French-speaking pediatric patients aged up to 18 years old with a history of upper or lower extremity DVT at least 6 months prior. RESULTS: Forward and backward translations were used to produce a pre-final French version of CAPTSure©, followed by cognitive debriefings in twenty participants (median age: 11.5 years, 55% male, median CAPTSure© score: 26). The participants felt that the questionnaire was thorough, with an adequate length. Eight out of fourteen (57%) items in the LE questionnaire and 7/12 (58%) of the items in the UE questionnaire were modified following participants' and a multidisciplinary expert committee's input, leading to the final French version of CAPTSure©. CONCLUSIONS: CAPTSure© was successfully adapted for French-speaking pediatric patients. This will ease the diagnosis and severity rating of PTS in children in clinical practice and allow international research collaborations for additional non-English-speaking patients.

Role of factor VIII, IX, and XI in venous thrombosis recurrence risk in adults and children: A systematic review.

Background: Predicting recurrent venous thromboembolic events (VTEs) is challenging in clinical practice for both adults and children, but it is relevant for clinical management. Identifying laboratory risk factors for VTE recurrence may aid in clinical decision-making. Objective: The goal of this systematic review is to investigate the predictive role of FVIII, IX, or XI in recurrent VTE in adult and pediatric patients with a first VTE. Methods: A systematic review of the published literature was conducted in databases MEDLINE In-Process, Other Nonindexed Citations, MEDLINE Epub Ahead of Print, EMBASE Classic + EMBASE (OvidSP), and Cochrane (Wiley). We included observational and interventional studies that comprised adults or children with a first VTE, FVIII, FIX, and/or FXI and objectively confirmed VTE recurrence. The quality in prognosis studies tool was used to assess the risk of bias. Results: We identified 2177 unique studies, of which 19 were included (18 for adults and 1 for children). The risk of bias was overall low to moderate. The studies were heterogenous with regards to population (provoked/unprovoked primary VTE), exposure (type of assay and cut-off values), and statistical analysis results (measures of association and modeling strategy). In adults, contradictory evidence was found for FVIII and FXI as outcome predictors, while no research could establish if FIX predicts VTE recurrence. Data in pediatrics were limited. Given the extensive heterogeneity of the literature, a meta-analysis was not performed. Conclusions: Overall, there is contradictory evidence that FVIII, FIX, or FXI predict recurrent VTE in adults and children. Addressing heterogeneity is a relevant aspect to consider in future studies investigating prognostic factors for VTE recurrence.

Divergence in brain size and brain region volumes across wild guppy populations.

Complex evolutionary dynamics have produced extensive variation in brain anatomy in the animal world. In guppies, Poecilia reticulata, brain size and anatomy have been extensively studied in the laboratory contributing to our understanding of brain evolution and the cognitive advantages that arise with brain anatomical variation. However, it is unclear whether these laboratory results can be translated to natural populations. Here, we study brain neuroanatomy and its relationship with sexual traits across 18 wild guppy populations in diverse environments. We found extensive variation in female and male relative brain size and brain region volumes across populations in different environment types and with varying degrees of predation risk. In contrast with laboratory studies, we found differences in allometric scaling of brain regions, leading to variation in brain region proportions across populations. Finally, we found an association between sexual traits, mainly the area of black patches and tail length, and brain size. Our results suggest differences in ecological conditions and sexual traits are associated with differences in brain size and brain regions volumes in the wild, as well as sexual dimorphisms in the brain's neuroanatomy.

Impact of deep vein thrombosis on adolescent athletes: Navigating an invisible disability.

Background: Injury in adolescent athletes that threatens their sport participation can result in a sense of identity loss during critical years for identity development, creating the potential for significant mental health challenges. The specific effect of deep vein thrombosis (DVT) in this vulnerable population has not been characterized. Purpose: To describe the impact of DVT diagnosis, treatment, and long-term complications on the mental well-being of athletes who sustained a DVT during adolescence and to identify strategies to improve the quality of care for these patients. Methods: Using a qualitative study design, athletes with a history of DVT during adolescence and their parents were recruited to participate in semistructured interviews. Interviews were transcribed and analyzed using thematic analysis. Participants were recruited until reaching thematic saturation. Results: In total, 19 participants (12 athletes, 7 parents) were recruited. Athletes were mainly males (67%), median age at time of DVT was 15 years (range, 12-18 years), and median age at study participation was 19 years (range, 16-34 years). Thematic analysis revealed four main themes: Theme 1: DVT posed a threat to sport participation; Theme 2: at a personal level, there were significant mental health challenges; Theme 3: at a societal level, DVT is an invisible disability; and Theme 4: physical, psychological, and transition support are important to improve the care of these patients. Conclusion: Deep vein thrombosis threatens an athlete's participation in sport, resulting in a significant and complex impact on their mental well-being. Heightened awareness and a multidisciplinary approach are needed to help young athletes navigate the consequences of DVT.

Age-Dependent Effects of Chronic Stress on Zebrafish Behavior and Regeneration.

Stress can have a significant impact on many aspects of an organism's physiology and behavior. However, the relationship between stress and regeneration, and how this relationship changes with age remains poorly understood. Here, we subjected young and old zebrafish to a chronic stress protocol and evaluated the impact of stress exposure on multiple measures of zebrafish behavior, specifically thigmotaxis (open field test) and scototaxis (light/dark preference test), and on regeneration ability after partial tail amputation. We found evidence that young and older adult fish are differentially impacted by stress. Only young fish showed a significant change in anxiety-like behaviors after being exposed to chronic stress, while their regeneration ability was not affected by the stress protocol. On the other hand, older fish regenerated their caudal fin significantly slower compared to young fish, but their behavior remained unaffected after being exposed to stress. We further investigated the expression of two candidate genes (nlgn1 and sam2) expressed in the central nervous system, and known to be associated with stress and anxiety-like behavior. The expression of stress-related gene candidate sam2 increased in the brain of older individuals exposed to stress. Our results suggest there is a close relationship between chronic stress, regeneration, and behavior in zebrafish (Danio rerio), and that the impact of stress is age-dependent.

Ubiquitin of Entamoeba histolytica induces antibody response in patients with invasive amoebiasis.

Entamoeba histolytica causes amoebic liver abscess (ALA) in humans. The injury of target cells by E. histolytica includes processes controlled by the ubiquitin Ehub. Previously, we found immunodominance of Ehub glycan moieties using immunized rabbits. In this work, we analysed dominance of antibodies to the glycoprotein Ehub in the sera from 52 patients with ALA. Controls were sera from 20 healthy people living in endemic areas with a high seroprevalence of antibodies to amoebas, and 20 patients with alcoholic hepatitis (AH) to rule out the cross-reaction of Ehub with autoantibodies induced by liver damage. Antigens were trophozoite extract, glycoprotein Ehub and the recombinant protein E. histolytica recombinant ubiquitin (rEhub). The sera from healthy volunteers and patients with AH do not have antibodies to glycoprotein Ehub. Surprisingly, only the antibodies from patients with ALA recognized the glycoprotein Ehub, and some sera gave a faint reaction with the recombinant protein, especially because evolutionarily, the ubiquitin is conserved between species. This is the first report demonstrating that antibodies to ubiquitin Ehub are induced exclusively in patients with invasive amoebiasis, and the antibody response is mainly to the glycoprotein, indicating glycans are immunodominant. Inhibitors of the Ehub glycans could be potential treatment for amoebiasis by selectively damaging trophozoites.

Upper-limit agricultural dietary exposure to streptomycin in the laboratory reduces learning and foraging in bumblebees.

In the past decade, the broadcast-spray application of antibiotics in US crops has increased exponentially in response to bacterial crop pathogens, but little is known about the sublethal impacts on beneficial organisms in agroecosystems. This is concerning given the key roles that microbes play in modulating insect fitness. A growing body of evidence suggests that insect gut microbiomes may play a role in learning and behaviour, which are key for the survival of pollinators and for their pollination efficacy, and which in turn could be disrupted by dietary antibiotic exposure. In the laboratory, we tested the effects of an upper-limit dietary exposure to streptomycin (200 ppm)-an antibiotic widely used to treat bacterial pathogens in crops-on bumblebee (Bombus impatiens) associative learning, foraging and stimulus avoidance behaviour. We used two operant conditioning assays: a free movement proboscis extension reflex protocol focused on short-term memory formation, and an automated radio-frequency identification tracking system focused on foraging. We show that upper-limit dietary streptomycin exposure slowed training, decreased foraging choice accuracy, increased avoidance behaviour and was associated with reduced foraging on sucrose-rewarding artificial flowers flowers. This work underscores the need to further study the impacts of antibiotic use on beneficial insects in agricultural systems.

Características clinicopatológicas de nódulos pulmonares: Experiencia en Clínica Reina Sofía, Bogotá, Colombia / Clinicopathological characteristics of pulmonary nodules: Experience at Clínica Reina Sofía, Bogotá, Colombia

Introducción. El cáncer de pulmón es la primera causa de mortalidad por cáncer a nivel mundial, lo que hace que sea considerado un problema de salud pública. Existen diferentes hallazgos imagenológicos que hacen sospechar la presencia de cáncer de pulmón, uno de los cuales son los nódulos pulmonares; sin embargo, estos también pueden verse en entidades benignas.Métodos. Se incluyeron 66 pacientes con biopsia de nódulo pulmonar en la Clínica Reina Sofía, en la ciudad de Bogotá, D.C., Colombia, entre el 1° de marzo del 2017 y el 28 de febrero del 2020. Se analizaron las características demográficas de los pacientes, las características morfológicas e histopatológicas de los nódulos pulmonares y la correlación entre sus características imagenológicas e histopatológicas. Resultados. El 69,2 % de los nódulos estudiados tenían etiología maligna, de estos el 55,5 % era de origen metástasico y el 44,5 % eran neoplasias primarias de pulmón, con patrón sólido en el 70,6 % de los casos. El patrón histológico más frecuente fue adenocarcinoma. Respecto a las características radiológicas, en su mayoría los nódulos malignos medían de 1 a 2 cm, de morfología lisa y distribución múltiple, localizados en lóbulos superiores. Conclusiones. La caracterización de los nódulos pulmonares brinda información relevante que orienta sobre los diagnósticos más frecuentes en nuestro medio, cuando se estudian nódulos sospechosos encontrados incidentalmente o en el seguimiento de otro tumor. Como el nódulo es la manifestación del cáncer temprano del pulmón, establecer programas de tamización que permitan el diagnóstico oportuno, es hoy día una imperiosa necesidad, para reducir la mortalidad.

Introduction. Lung cancer is the leading cause of cancer mortality worldwide, which makes it a public health problem. There are different imaging findings that suggest the presence of lung cancer, one of which is pulmonary nodules; however, these can also be seen in benign entities. Methods. A total of 66 patients with pulmonary nodule biopsy at Clínica Reina Sofía, in the city of Bogotá D.C. were included between March 1, 2017 and February 28, 2020. The demographic characteristics of the patients, the morphologic and histopathologic characteristics of the pulmonary nodules and their correlation with their pathological diagnosis were analyzed.Results. 69.2% of the nodules studied had malignant etiology, of these 55.5% were of metastatic origin, and 44.5% were primary lung neoplasms, with a solid pattern in 70.6% of the cases. The most frequent histological pattern was adenocarcinoma. Regarding the radiological characteristics, most of the malignant nodules measure 1 to 2 cm, of smooth morphology and had multiple distribution, located in the upper lobes. Conclusions. The characterization of pulmonary nodules provides relevant information that guides the most fre-quent diagnoses in our setting, when suspicious nodules found incidentally or in the follow-up of another tumor are studied. As the nodule is the manifestation of early lung cancer, establishing screening programs that allow timely diagnosis is an urgent need to reduce mortality.

Lipids fluctuations in mosquitoes upon arboviral infections.

Arboviruses are responsible for several emerging and re-emerging infectious diseases, with dengue, Zika virus disease and Chikungunya fever being the most important arboviral diseases nowadays. Infection of these viruses depends primarily on its ability to replicate and disseminate in mosquitoes. Since these viruses are enveloped, viral replication, assembly and release occurs in the cellular membranes, which depends on the manipulation of host lipid metabolism. Specifically in mammalian cells replication, they use host lipids to establish a compartment known as replication complex that contains the replicase complex. This complex includes viral RNA, proteins and host factors necessary for a successful replication in mammalian cells. Although little is known about extrinsic factor(s) needed for arbovirus replication in vectors,recent reports show that high lipid concentrations are related with increased viral replication in mosquito cells infected with dengue, Zika and Chikungunya viruses. Here, we present a review that focuses on the cellular mechanisms and the lipid environment alteration in mosquito vector after arbovirus infection and their relationship with arbovirus replication.

Characteristics of upper- and lower-extremity deep vein thrombosis and predictors of postthrombotic syndrome in children.

Our understanding of postthrombotic syndrome (PTS) predictors in children is evolving. The present study aimed to investigate differences in patient- and deep vein thrombosis (DVT)-related characteristics between central venous catheter (CVC)-related and non-CVC-related thrombosis in children, as well as early PTS predictors. Children aged 0 to 18 years were prospectively recruited ≥6 months after imaging-proven upper- or lower-extremity DVT. PTS was measured using CAPTSure. Early predictors included age at DVT diagnosis, DVT symptoms, DVT burden, and days on therapeutic anticoagulation within 30 days post-DVT diagnosis. Analysis of predictors was stratified by CVC-related and non-CVC-related thrombosis. Generalized estimating equations were used for data analyses. In total, 313 DVT-affected extremities of 256 patients were assessed; 275 (88%) DVT cases were CVC related. Patients with non-CVC-related thrombosis were older (median age, 5.8 years; 25th-75th percentile, 4.9-6.4 years vs 3.5 months; 25th-75th percentile, 0.7-18.7 months; P < .001) and more likely to have thrombophilia (64% vs 22%; P < .001) and obesity (30% vs 13%; P = .01) than patients with CVC-related thrombosis. CAPTSure scores were 9.5 points higher (standard error, 3.0; P = .02) in the non-CVC-related thrombosis stratum. Age at the time of DVT predicted PTS in both strata; DVT burden and time from DVT diagnosis to PTS assessment predicted PTS in CVC-related thrombosis. In sum, PTS severity was higher in non-CVC-related vs CVC-related thrombosis. Increasing age at the time of DVT was associated with higher PTS severity. DVT burden and time from DVT diagnosis to PTS assessment were significant PTS predictors in CVC-related thrombosis, indicating that long-term follow-up of these children is important.

Analysis of Caloric and Noncaloric Sweeteners Present in Dairy Products Aimed at the School Market and Their Possible Effects on Health.

Over the past decades, Mexico has become one of the main sweetener-consuming countries in the world. Large amounts of these sweeteners are in dairy products aimed at the children's market in various presentations such as yogurt, flavored milk, flan, and cheeses. Although numerous studies have shown the impact of sweeteners in adults, the current evidence for children is insufficient and discordant to determine if these substances have any risk or benefit on their well-being. Therefore, this study aimed to describe the sweeteners present in 15 dairy products belonging to the school-age children's market in Mexico and their impact on health. These dairy products were selected through a couple of surveys directed at parents of school-age children. After that, the list of ingredients of each product was analyzed to identify their sweetener content. From there, exhaustive bibliographic research on sweeteners and their possible health effects was carried out, which included 109 articles and 18 studies. The results showed that at a neurological, endocrinological, cardiovascular, metabolic, osseous, renal, hepatic, dental, reticular, carcinogenic, and gut microbiota level; sucrose, fructose, high-fructose corn syrup, maltodextrins, sucralose, and acesulfame K, have a negative effect. While maltodextrins, stevia, polydextrose, and modified starch have a positive one. For these reasons, it is necessary to evaluate the advantages and disadvantages that the consumption of each sweetener entails, as well as a determination of the appropriate acceptable daily intake (ADI).

Compression garments for the management of pediatric post-thrombotic syndrome: A prospective longitudinal study.

BACKGROUND: Graduated compression garments (CG) are a standard form of management of post-thrombotic syndrome (PTS) in adults, but data in children are lacking. OBJECTIVES: We aimed to study the attitudes toward CG and change in PTS severity score in children who were prescribed CG for PTS management. METHODS: Children with PTS were enrolled in this longitudinal prospective study at the time of CG prescription. PTS severity was measured at baseline and follow-up using CAPTSure© ; attitude toward CG was registered at follow-up. RESULTS: Forty-five patients were enrolled (median age 13 years, 25th-75th percentile 8-15 years; 53% male patients); 71% were prescribed socks and 29% sleeves; pressure was 15-20 mmHg in 84% of CG. Median baseline PTS CAPTSure© score was 31 points (25th-75th percentile 21-45 points). At follow-up, 49% of patients found CG helpful, 27% found CG not helpful, and 16% did not buy or wear the CG. Eight percent of enrolled patients did not return for study follow-up. Ninety-five percent of the children who found CG helpful wore them for ≥3 days/week. Hours of CG wear at the time of follow-up were associated with lower PTS scores at follow-up in a non-linear manner (e.g., wearing 12 vs. 0 h/day was associated with a 16-point reduction in PTS scores at follow-up, 95% CI -29 to -2 points). CONCLUSION: Nearly half the patients who were prescribed CG found them helpful. We observed non-linear improvement in PTS severity with the use of low-pressure CG for 8-12 h/day and ≥3 days/week, providing guidance in their prescription.

Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery.

Bacterial resistance to antibiotics makes previously manageable infections again disabling and lethal, highlighting the need for new antibacterial strategies. In this regard, inhibition of the bacterial division process by targeting key protein FtsZ has been recognized as an attractive approach for discovering new antibiotics. Binding of small molecules to the cleft between the N-terminal guanosine triphosphate (GTP)-binding and the C-terminal subdomains allosterically impairs the FtsZ function, eventually inhibiting bacterial division. Nonetheless, the lack of appropriate chemical tools to develop a binding screen against this site has hampered the discovery of FtsZ antibacterial inhibitors. Herein, we describe the first competitive binding assay to identify FtsZ allosteric ligands interacting with the interdomain cleft, based on the use of specific high-affinity fluorescent probes. This novel assay, together with phenotypic profiling and X-ray crystallographic insights, enables the identification and characterization of FtsZ inhibitors of bacterial division aiming at the discovery of more effective antibacterials.

Diagnostic value of D-dimers for limb deep vein thrombosis in children: A prospective study.

The present study sought to evaluate the discriminative and predictive ability of D-dimer for pediatric limb DVT. Children aged 28 days-18 years requiring imaging to rule out limb DVT, as per the treating clinical team, were enrolled in the study. The outcome was ultrasound proven DVT. The D-dimer levels were obtained around the time of imaging. Receiver operating characteristic (ROC) curves and logistic regression models were used for data analyses. In total, 296 patients were enrolled between 2017-2020; 204 patients were diagnosed with DVT (DVT[+]). Median D-dimer levels were 2.3 µg/ml FEU (25th-75th percentile 0.9-3.9) among DVT(+) and 1.9 µg/ml FEU (25th-75th percentile 0.8-4.0) among DVT(-) patients (p = 0.60). The area under the ROC curve (AUC) was 0.52 (95% confidence interval [CI] 0.45-0.59). The odds ratio for D-dimer levels was 1.00 (95% CI 0.99-1.01), holding confounders constant. In a sub-group exploratory analysis including 23 patients with no underlying conditions or co-morbidities, the AUC curve was 0.90 (95% CI 0.76-1.00). In conclusion, in this prospective cohort study of consecutive children with suspected limb DVT, D-dimer levels had poor discriminative and predictive ability for DVT. However, D-dimer levels showed better discriminative and predictive ability for DVT in an exploratory sample of patients with no underlying conditions or co-morbidities at the time of diagnosis.