IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia.

Background: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL. Methods: A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation. Results: We identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed. Discussion: Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.

Stable Laboratory Culture System for the Ctenophore Mnemiopsis leidyi.

Ctenophores are marine organisms attracting significant attention from evolutionary biology, molecular biology, and ecological research. Here, we describe an easy and affordable setup to maintain a stable culture of the ctenophore Mnemiopsis leidyi. The challenging delicacy of the lobate ctenophores can be met by monitoring the water quality, providing the right nutrition, and adapting the handling and tank set-up to their fragile gelatinous body plan. Following this protocol allows stable laboratory lines, a continuous supply of embryos for molecular biological studies, and independence from population responses to environmental fluctuations.

Influence of Bentonite Particles on the Mechanical Properties of Polyester-Sisal Fiber Composites.

As a part of the mission to create materials that are more environmentally friendly, we present the following proposal, in which a study of the mechanical properties of composite materials comprising a polyester resin with sisal fiber and bentonite particles was conducted. Sisal fiber was added to a matrix in percentages ranging from 5% to 45% in relation to the polyester resin weight, while bentonite remained fixed at 7% in relation to the polyester resin weight. The specimens were manufactured by compression molding. The mechanical properties were analyzed by tensile, bending, impact, stepped creep, and relaxation tests. In addition, energy-dispersive X-ray spectroscopy and scanning electron microscopy analyses were carried out to analyze the composition and heterogeneity of the structure of the composite material. The results obtained showed that 7% of bentonite added to the matrix affects the tensile strength. Flexural strength increased by up to 21% in the specimens with a 20% addition of sisal fiber, while the elastic modulus increased by up to 43% in the case of a 20% addition of sisal fiber. The viscoelastic behavior was improved, while the relaxation stress was affected.

Infections and risk factors for infection-related mortality after pediatric allogeneic hematopoietic stem cell transplantation in Mexico: A single center retrospective study.

OBJECTIVE: To identify the type of infections and risk factors for infection-related mortality (IRM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective cohort study of patients <16 years of age treated in 2010-2019 was conducted. Unadjusted hazard ratios (HR) and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CIs) were estimated using Cox regression. Cumulative incidence was calculated. RESULTS: Data for 99 pediatric patients were analyzed. The myeloablative conditioning was the most used regimen (78.8%) and the hematopoietic stem cell source was predominantly peripheral blood (80.8%). Primary graft failure occurred in 19.2% of patients. Frequency of acute graft-versus-host disease was 46.5%. Total of 136 infectious events was recorded, the most common of which were bacterial (76.4%) followed by viral infection (15.5%) and then fungal infection (8.1%). The best predictors for infection subtypes where the following: a) for bacterial infection (the age groups of 10.1-15 years: aHR = 3.33; 95% CI: 1.62-6.85 and. >15 years: aHR = 3.34; 95% CI: 1.18-9.45); b) for viral infection (graft versus host disease: aHR = 5.36; 95% CI: 1.62-17.68), however, for fungal infection statistically significant predictors were not identified. Related mortality was 30% (n = 12). Increased risk for infection-related mortality was observed in patients with unrelated donor and umbilical cord stem cells recipients (HR = 3.12; 95% CI: 1.00-9.85). CONCLUSIONS: Frequencies of infections and infection-related mortality appear to be similar to those reported. Unrelated donors and stem cells from umbilical cord recipients were associated with a high risk of mortality.

Odd family reunion: DNA barcoding reveals unexpected relationship between three hydrozoan species.

Knowledge of life histories is crucial for understanding ecological and evolutionary processes, but for many hydrozoan species only incomplete life cycles have been described due to challenges in linking hydromedusae with their polyp stages. Using a combination of DNA barcoding, morphology, and ecological information, we describe for the first time the polyp stage of Halopsis ocellata Agassiz, 1865 and re-describe that of Mitrocomella polydiademata (Romanes, 1876). Campanulinid hydroids referable to Lafoeina tenuis Sars, 1874 and collected in the same biogeographic region as the type locality of this species are shown to be the polyp stage of these two mitrocomid hydromedusae. The nominal species L. tenuis thus is a species complex that includes the polyp stage of medusae belonging to at least two genera currently placed in a different family. Consistent morphological and ecological differences were found between the polyps linked to each of these two hydromedusae, but molecular results suggest that yet other species may have morphologically similar hydroids. Polyps morphologically identified to L. tenuis are therefore better referred to as Lafoeina tenuis-type until further associations are resolved, particularly when occurring outside of the area of distribution of H. ocellata and M. polydiademata. Molecular identification integrated with traditional taxonomy is confirmed as an effective approach to link inconspicuous stages of marine invertebrates with hitherto unknown life cycles, especially in often-overlooked taxa. Disentangling the relationships between L. tenuis, H. ocellata, and M. polydiademata lays the ground for future research aimed at resolving the taxonomy and systematics of the enigmatic families Mitrocomidae and Campanulinidae.

Syncytial nerve net in a ctenophore adds insights on the evolution of nervous systems.

A fundamental breakthrough in neurobiology has been the formulation of the neuron doctrine by Santiago Ramón y Cajal, which stated that the nervous system is composed of discrete cells. Electron microscopy later confirmed the doctrine and allowed the identification of synaptic connections. In this work, we used volume electron microscopy and three-dimensional reconstructions to characterize the nerve net of a ctenophore, a marine invertebrate that belongs to one of the earliest-branching animal lineages. We found that neurons in the subepithelial nerve net have a continuous plasma membrane that forms a syncytium. Our findings suggest fundamental differences of nerve net architectures between ctenophores and cnidarians or bilaterians and offer an alternative perspective on neural network organization and neurotransmission.

Effect of Nanometric Particles of Bentonite on the Mechanical Properties of a Thermoset Polymeric Matrix Reinforced with Hemp Fibers.

The influence of the addition of bentonite nanoparticles on the tensile and flexural strength of a thermosetting polymer matrix composite material reinforced with hemp fibers was de-terminated. All composites were manufactured with 5% of bentonite in the polymer mass-weight ratios and 10 to 45 wt% of fibers with a step of 5%. For mechanical characterization, tensile and flexural tests were performed: scanning electron microscopy and energy-dispersive X-ray spectroscopy analyses were carried out. The tensile strength of the samples containing bentonite compared to the polymer samples with the fiber addition was affected for all fiber addition percentages, except for 35% while the flexural resistance improved with the addition of bentonite in the percentages of 20, 30, 35, and 45% of fiber addition. With the addition of bentonite, the maximum values of tensile and flexural strength were both obtained for the 35% addition of fibers, with values of 34.28 MPa and 98.04 MPa, respectively. The presence of bentonite favored the rigidity of the material to traction and bending, which was reflected through an increase in the elastic modulus compared to the composite that only had fiber. The maximum values obtained were 9065 MPa in tension and 8453 MPa in flexion for the 40% and 35% of addition of fiber, respectively. Microscopy showed a good distribution of fibers in the matrix, the absence of internal porosities, and a good interaction between matrix and reinforcement.

Parameter Identification of Fractional Index Viscoelastic Model for Vegetable-Fiber Reinforced Composite.

In the present work, parameters for adapting the behavior of the uniaxial three-element viscoelastic constitutive model with integer and fractional index derivatives to the mechanical evolution of an epoxy-composite material reinforced with long random henequen fibers, were determined. Cyclic loading-unloading with 0.1%, 0.2%, 0.3%, …, 1.0% controlled strain and staggered fluency experiments at 5 MPa, 10 MPa, and 15 MPa constant tension were performed in stages, and the obtained data were used to determine and validate the model's parameter values. The Inverse Method of Identification was used to calculate the parameters, and the Particle Swarm Optimization (PSO) method was employed to achieve minimization of the error function. A comparison between the simulated uniaxial results and the experimental data is demonstrated graphically. There exists a strong dependence between properties of the composite and the fiber content (0 wt%, 9 wt%, 14 wt%, 22 wt%, and 28 wt% weight percentage fiber/matrix), and therefore also of the model parameter values. Both uniaxial models follow the viscoelastic behavior of the material and the fractional index version presents the best accuracy. The latter method was noted to be adequate for determination of the aforementioned constants using non-large experimental data and procedures that are easy to implement.

Tuberculosis cutánea esporotricoide en la Amazonía peruana: reporte de caso / Sporotrichoid cutaneous tuberculosis in the peruvian amazon: case report

RESUMEN La tuberculosis cutánea es una presentación rara de la infección por Mycobacterium tuberculosis. Se presenta el caso de una mujer sin antecedentes médicos de importancia, con un tiempo de enfermedad de año y medio, caracterizado por lesiones tipo esporotricoide, con diseminación linfocutánea en miembro superior derecho, de evolución lentamente progresiva. Se realizó un estudio histopatológico encontrándose células gigantes tipo Langhans y escasa necrosis. El paciente recibió terapia de esquema sensible antituberculoso, con evolución favorable.

ABSTRACT Cutaneous tuberculosis is a rare presentation of Mycobacterium tuberculosis infection. We present the case of a woman without important medical history, with a disease period of one year and a half, characterized by sporotrichoid-like lesions, with lymphocutaneous dissemination in the right upper limb, and with slowly progressive evolution. The histopathological tests revealed Langhans type giant cells and scarce necrosis. The patient received therapy with a sensitive antituberculous scheme, and evolved favorably.

Reversible cerebral vasoconstriction syndrome in children: an update.

Headaches are one of the most common neurologic complaints leading to emergency room visits in pediatric patients. Of the different type of headache presentations, thunderclap headaches require a particularly urgent work-up. In children, recurrent thunderclap headaches are more often associated with reversible cerebral vasoconstriction syndrome (RCVS) than other etiologies such as subarachnoid hemorrhage. RCVS is a vascular disorder of incompletely understood etiology, characterized by diffuse vasoconstriction of the cerebral arterial vasculature, and commonly associated with recurrent severe headaches. Patients may experience focal neurological deficits, due to hemorrhages, infarcts, and even posterior reversible encephalopathy syndrome . Although RCVS has been best characterized in adults, it does occur in children. This review summarizes the presentation of RCVS in children and highlights some of the differences with the adult population.

Neuropeptide repertoire and 3D anatomy of the ctenophore nervous system.

Ctenophores are gelatinous marine animals famous for locomotion by ciliary combs. Due to the uncertainties of the phylogenetic placement of ctenophores and the absence of some key bilaterian neuronal genes, it has been hypothesized that their neurons evolved independently. Additionally, recent whole-body, single-cell RNA sequencing (scRNA-seq) analysis failed to identify ctenophore neurons using any of the known neuronal molecular markers. To reveal the molecular machinery of ctenophore neurons, we have characterized the neuropeptide repertoire of the ctenophore Mnemiopsis leidyi. Using the machine learning NeuroPID tool, we predicted 129 new putative neuropeptide precursors. Sixteen of them were localized to the subepithelial nerve net (SNN), sensory aboral organ (AO), and epithelial sensory cells (ESCs), providing evidence that they are neuropeptide precursors. Four of these putative neuropeptides had a behavioral effect and increased the animals' swimming speed. Intriguingly, these putative neuropeptides finally allowed us to identify neuronal cell types in single-cell transcriptomic data and reveal the molecular identity of ctenophore neurons. High-resolution electron microscopy and 3D reconstructions of the nerve net underlying the comb plates confirmed a more than 100-year-old hypothesis of anastomoses between neurites of the same cell in ctenophores and revealed that they occur through a continuous membrane. Our work demonstrates the unique ultrastructure of the peptidergic nerve net and a rich neuropeptide repertoire of ctenophores, supporting the hypothesis that the first nervous system(s) evolved as nets of peptidergic cells.

A Case of Pediatric Stroke: Osteosarcoma Embolus in the Internal Carotid Artery.

Stroke in the pediatric population is rare. Despite presentation similar to that seen in the adult patient, the diagnosis in a child can be missed or mistaken for a more common stroke mimic. Due to its rarity, there are no completed pediatric clinical trials investigating best treatment, though guidelines have been extrapolated from adult guidelines and retrospective cohort studies to include some combination of thrombolysis and mechanical thrombectomy. Rarer still is pediatric stroke caused by tumor embolus. We present the case of a young child diagnosed with stroke secondary to osteosarcoma embolism to the left internal carotid artery and review the relevant literature to discuss the considerations and challenges of treatment of stroke in the pediatric population.

Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brain.

Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRß) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRß in adult V-SVZ NSCs leads to their release from quiescence, uncovering gliogenic domains for different glial cell types. These domains are also recruited upon injury. We identify an intraventricular oligodendrocyte progenitor derived from NSCs inside the brain ventricles that contacts supraependymal axons. Together, our findings reveal that the adult V-SVZ contains spatial domains for gliogenesis, in addition to those for neurogenesis. These gliogenic NSC domains tend to be quiescent under homeostasis and may contribute to brain plasticity.

Relationship between the history of cerebrovascular disease and mortality in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Past history of stroke has been associated with an increased risk of a new ischemic stroke. Several studies have indicated increased prevalence of strokes among coronavirus patients. However, the role of past history of stroke in COVID19 patients is still unclear. The purpose of this systematic review is to evaluate and summarize the level of evidence on past history of stroke in COVID19 patients. METHODS: A systematic review was performed according to the PRISMA guidelines was performed in PubMed, Embase, EBSCO Host, Scopus, Science Direct, Medline, and LILACS. Eligibility criteria: We evaluated studies including patients with diagnosis of COVID 19 and a past history of stroke. Risk of bias: was evaluated with the Newcastle- Ottawa Scale (NOS) and experimental studies were evaluated using the ROBINS-I scale. RESULTS: Seven articles out of the total 213 articles were evaluated and included, involving 3244 patients with SARS VOC 2 Disease (COVID19) of which 198 had a history of cerebrovascular disease. Meta-analysis of the data was performed, observing an increase in mortality in patients with a history of cerebrovascular disease compared to those with different comorbidities or those without underlying pathology (OR 2.78 95 % CI [1.42-5.46] p = 0.007; I2 = 49 %) showing adequate heterogeneity. The presence of publication bias was evaluated using the Egger test in a funnel plot, showing adequate. Asymmetry, indicating that there is no publication bias; however, due to the low number of included studies, we could not rule out or confirm the presence of bias. CONCLUSIONS: The history of cerebrovascular disease was associated with a 2.78-fold increased risk of mortality compared to patients with other comorbidities or without underlying pathologies.

Metacognition of daily self-regulation processes and personality traits in borderline personality disorder.

BACKGROUND: Patients with Borderline Personality Disorder (BPD) are characterized by impoverished self-regulatory mechanisms and self-image distortions. An intriguing question is to what extent BPD individuals develop accurate perceptions of their self-regulatory everyday functioning. Here, we tackle this issue evaluating their metacognitive abilities. METHODS: One hundred and forty-four participants were enrolled in the study and divided into a BPD group and a healthy Control group, with each consisting of 36 participants paired with their corresponding close relatives. We compared self-report evaluations of the participants' self-regulatory processes in daily-life activities and personality traits with external perceptions by close relatives, as a measure of metacognition. The ratings from participants and their informants were compared using an ANCOVA profile analysis. RESULTS: Self-report results showed poor self-regulation ability in the daily environment as well as extreme scores in personality-traits in the BPD group in comparison with healthy participants. Further, in the BPD group we found a clear discrepancy between the information provided by patients and their close relatives regarding the processes involved in self-regulation of daily-life activities (but not for personality traits). This discrepancy was related to their clinical status and was not observed in the healthy control group. LIMITATIONS: Analysis was based on self-report data, focusing on the difference with informants reports only. Conclusions about the direction of a possible bias on participants' self-perception are limited. CONCLUSIONS: Metacognitive deficits might play a key mediating role between the altered cognitive processes responsible for self-regulation and cognitive control and the daily-life consequences in BPD.