Lattice Boltzmann simulation of deformable fluid-filled bodies: progress and perspectives.

With the rapid development of studies involving droplet microfluidics, drug delivery, cell detection, and microparticle synthesis, among others, many scientists have invested significant efforts to model the flow of these fluid-filled bodies. Motivated by the intricate coupling between hydrodynamics and the interactions of fluid-filled bodies, several methods have been developed. The objective of this review is to present a compact foundation of the methods used in the literature in the context of lattice Boltzmann methods. For hydrodynamics, we focus on the lattice Boltzmann method due to its specific ability to treat time- and spatial-dependent boundary conditions and to incorporate new physical models in a computationally efficient way. We split the existing methods into two groups with regard to the interfacial boundary: fluid-structure and fluid-fluid methods. The fluid-structure methods are characterised by the coupling between fluid dynamics and mechanics of the flowing body, often used in applications involving membranes and similar flexible solid boundaries. We further divide fluid-structure-based methods into two subcategories, those which treat the fluid-structure boundary as a continuum medium and those that treat it as a discrete collection of individual springs and particles. Next, we discuss the fluid-fluid methods, particularly useful for the simulations of fluid-fluid interfaces. We focus on models for immiscible droplets and their interaction in a suspending fluid and describe benchmark tests to validate the models for fluid-filled bodies.

Population Pharmacokinetic of the Diterpenes ent-Polyalthic Acid and Dihydro-ent-Agathic Acid from Copaifera Duckei Oil Resin in Rats.

Copaifera duckei oleoresin is a plant product extensively used by the Brazilian population for multiple purposes, such as medicinal and cosmetic. Despite its ethnopharmacological relevance, there is no pharmacokinetic data on this important medicinal plant. Due to this, we determined the pharmacokinetic profile of the major nonvolatile compounds of C. duckei oleoresin. The diterpenes ent-polyalthic acid and dihydro-ent-agathic acid correspond to approximately 40% of the total oleoresin. Quantification was performed using LC-MS/MS, and the validated analytical method showed to be precise, accurate, robust, reliable, and linear between 0.57 and 114.74 µg/mL plasma and 0.09 to 18.85 µg/mL plasma, respectively, for ent-polyalthic acid and dihydro-ent-agathic acid, making it suitable for application in preclinical pharmacokinetic studies. Wistar rats received a single 200 mg/kg oral dose (gavage) of C. duckei oleoresin, and blood was collected from their caudal vein through 48 h. Population pharmacokinetics analysis of ent-polyalthic and dihydro-ent-agathic acids in rats was evaluated using nonlinear mixed-effects modeling conducted in NONMEN software. The pharmacokinetic parameters of ent-polyalthic acid were absorption constant rate = 0.47 h-1, central and peripheral apparent volume of distribution = 0.04 L and 2.48 L, respectively, apparent clearance = 0.15 L/h, and elimination half-life = 11.60 h. For dihydro-ent-agathic acid, absorption constant rate = 0.28 h-1, central and peripheral apparent volume of distribution = 0.01 L and 0.18 L, respectively, apparent clearance = 0.04 L/h, and elimination half-life = 3.49 h. The apparent clearance, central apparent volume of distribution, and peripheral apparent volume of distribution of ent-polyalthic acid were approximately 3.75, 4.00-, and 13.78-folds higher than those of dihydro-ent-agathic.

Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.

BACKGROUND: The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRß in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown. RESULTS: Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety. CONCLUSIONS: These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.

Feline sporotrichosis: Characterization of cutaneous and extracutaneous lesions using different diagnostic methods.

Sporotrichosis is a mycotic infection of the cutaneous and subcutaneous tissues caused by Sporothrix spp. that can also cause extracutaneous manifestations. This study aimed to characterize cutaneous and extracutaneous sporotrichosis lesions in cats. Over 1 year, 102 cats rescued by the Zoonoses Control Center of Belo Horizonte, Brazil, euthanized with clinical suspicion of feline sporotrichosis were evaluated. After euthanasia, the animals were evaluated by macroscopic, cytological, histopathological, and immunohistochemistry (IHC) examinations; fungal culture; and polymerase chain reaction (PCR). Sporothrix infection was identified by at least one diagnostic technique in all cats (n = 102) evaluated by postmortem examination, including 26/28 cases (93%) evaluated by IHC, 66/90 cases (73%) evaluated by cytology, 70/102 cases (68.6%) evaluated by histopathology, and 62/74 cases (84%) evaluated by fungal culture. Two cats had positive results only by fungal culture. Cytology and histopathology examinations were effective in diagnosing sporotrichosis, although IHC was needed to confirm the diagnosis in cats with low fungal loads. Sporothrix brasiliensis was confirmed by the sequencing of 3 samples. Skin lesions were characterized mainly by pyogranulomatous to granulomatous dermatitis (frequently with subcutaneous inflammation) with different intensities of Sporothrix spp. yeast. Extracutaneous findings associated with sporotrichosis included rhinitis or rhinosinusitis, lymphadenitis, pneumonia, meningitis, periorchitis, conjunctivitis, and glossitis. Extracutaneous infections were observed in 74/102 cases, and a possible association between the chronicity of the disease and the higher pathogenicity of this fungal species in cats requires further investigation.

Ecological aspects of sand fly fauna (Diptera: Psychodidae, Phlebotominae) of Sumidouro District, State of Rio de Janeiro, Brazil.

Aiming to compare and update the sand fly fauna of Portão de Pedra site, Sumidouro District, Rio de Janeiro State, Brazil, and considering the environmental changes occurred, the biology and ecology of the local sandfly species were examined five years later as a complementary study carried. Captures were made in the cave, surroundings of cave and forest of the region, from 6 p.m. to 6 a.m. Among the 2323 sandflies of eigth species of the Lutzomyia were captured: L. gasparviannai, L. edwardsi, L. tupynambai, L. hirsuta, L. whitmani, L. migonei, L. intermedia, Lutzomyia. sp and one species of the Brumptomyia Kind: B. brumpti. In 2009 and 2010 were collected 1756 samples from ten species of the former genus and two of the second. L. gasparviannai was predominant, in the three collection sites, in both periods. Five species implicated as vectors of Leishmania: L. intermedia, L. whitmani, L. migonei, L. hirsuta and L. davisi have been collected in the area. Poisson regression and ANOVA were used to perform statistical analysis of species most relevant. The record of L. intermedia and a case of American tegumentary leishmaniasis are relevant to the public health of municipality and of state of Rio de Janeiro.

Polyprenylated Benzophenones from Brazilian Red Propolis: Analytical Characterization and Anticancer Activity.

The present work describes the extraction of a polyprenylated benzophenone-rich extract from Brazilian red propolis (ERPB), the development and validation of an RP-HPLC-UV method to characterize it, and its evaluation against breast cancer cell lines MCF-7 and MDA-MB-231, as well as the normal counterpart MCF-10A. A mixture of gutifferone E and xanthochymol (1+2), and isolated oblongifolin B (3) were used as chemical standards for ERPB and were also evaluated. The concentrations of 1+2 and 3 corresponded to 16.68% and 42.25% of the total content of the extract, respectively, and the validation parameters evaluated were satisfactorily met. The cytotoxic effects of ERPB were assessed, and the obtained IC50 values were 19.58 µg/mL (MCF-10A), 11.56 µg/mL (MCF-7), and 5.22 µg/mL (MDA-MB-231). In conclusion, ERPB exhibits promising cytotoxic effects on the tested breast cell lines. However, further investigation to elucidate its potential therapeutic applications and safety profile should be conducted.

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Evaluation of pulp chamber temperature during cementation with the preheated composite resin technique.

STATEMENT OF PROBLEM: The cementation technique using preheated composite resin requires high temperatures for optimal execution and may lead to increased and damaging intrapulpal temperatures. Whether the technique can lead to a temperature increase that might lead to necrosis of the pulp tissue is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the temperature variation in the pulp chamber of bovine teeth with veneer-type preparations during veneer cementation using the preheated composite resin technique. MATERIAL AND METHODS: A total of 103 bovine incisors were divided into 8 groups (n=10) and prepared for indirect veneers with different preparation depths: 2.0 mm, 1.5 mm, 1.0 mm, and 0.5 mm. Veneers were cemented on these preparations using 2 cementation protocols: preheated composite resin and photopolymerizable resin cement. The teeth were attached to a device containing a temperature sensor which was inserted into the pulp chamber to quantify the intrapulpal temperature variation produced during the cementation protocols. The data were analyzed using a statistical software program. The level of statistical significance for the analyses was with a confidence interval of 95%, sampling power of 80%, and a moderate effect size (0.36). RESULTS: The groups cemented with preheated composite resin and the groups with the greatest preparation depth had the highest mean intrapulpal temperature; the PHC2 group presented a mean ±standard deviation temperature increase of 5.70 ±2.14 °C. CONCLUSIONS: The heat generated by heating the resin contributed to the increase in intrapulpal temperature. Temperature variations were greater in deeper preparations, especially when preheated resin technique was used.

Effects of the self-perceived sensorimotor demand and immersion during video gaming on visual-attention skills.

Playing specific genres of video games (e.g., action video games) has been linked to improvements in cognitive skills mostly related to attentional phenomena. Nonetheless, do video games have features or dimensions in common that impact cognitive improvements beyond the game genre? Here, we argue that the sensorimotor demand-the amount of demand for precise coordination between movement and perception-is a key element in the improvements associated with playing video games. We conducted a two-part study to test this hypothesis: a self-report online gaming instrument development and validation and an in-lab behavioural and electrophysiological study. In the first study, data from 209 participants were used to devise the sensorimotor demand instrument (SMDI). The SMDI was split into three dimensions of video game playing: sensorimotor contingency, immersion and unfocused gaming. Criterion validity related to video gamers' characteristics supported that the SMDI is sensitive to the input device (e.g., keyboard or touchscreens), and the most recent experience gained during gaming sessions while not being sensitive to the game genre. In the second study, data from 20 participants who performed four visual-attentional tasks previously reported in the literature showed that the SMDI's dimensions were associated with behavioural performance measures and the latency and amplitude of event-related potentials (N1, P2 and P3). Despite the challenge of studying the video gamer population, our study remarks on the relevance of sensorimotor demands in the performance of attentional tasks and its potential use as a dimension to characterize the experience of playing video games beyond the game genre.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Quantifying physiologic parameters of the gastroesophageal junction during robotic sleeve gastrectomy and identifying predictors of post-sleeve gastroesophageal reflux disease.

BACKGROUND: Sleeve gastrectomy is among the most commonly-performed procedures for morbid obesity. However, patients occasionally develop post-sleeve gastroesophageal reflux disease (GERD). Identifying patients most at risk for this complication remains difficult. We aimed to correlate intra-operative physiologic measurements of the lower esophageal sphincter (LES) at the gastroesophageal junction (GEJ) during robotic sleeve gastrectomy in an attempt to identify predictors of post-sleeve GERD symptoms. METHODS: A retrospective chart review of a prospectively maintained database identified 28 patients in whom robotic sleeve gastrectomy was performed utilizing EndoFLIP™ technology between January and September 2021. Intraoperative LES measurements at the GEJ including cross-sectional area (CSA), distensibility index (DI), intra-balloon pressure, and high-pressure zone (HPZ length) were correlated with post-operative GERD. RESULTS: GEJ CSA, pressure, and DI increased over the course of the surgery (CSA pre-op: 31 (IQR 19.3-39.5) mm2 vs. post-op: 67 (IQR 40.8-95.8) mm2, p < 0.001; pressure: 25.8 (IQR 20.2-33.1) mmHg vs. 31.5 (IQR 28.9-37.0) mmHg, p = 0.007; DI 1.1 (IQR 0.8-1.8) mm2/mmHg vs. 2.0 (IQR 1.2-3.0) mm2/mmHg, p = < 0.001), whereas HPZ length decreased (2.5 (IQR 2.5-3) cm vs. 2.0 (IQR 1.3-2.5) cm, p = 0.022). Twenty-three patients (82.1%) completed a post-operative GERD questionnaire. Fifteen (65.2%) had no GERD symptoms before or after surgery; 5 (21.7%) reported new post-sleeve GERD symptoms; 3 (13.0%) reported exacerbation of pre-existing GERD symptoms. Patients with new or worsening GERD symptoms had higher post-sleeve DIs (3.2 (IQR 1.9-4.5) mm2/mmHg vs. 1.5 (IQR 1.2-2.4) mm2/mmHg, p = 0.024) and lower post-sleeve LES pressures (29.9 (IQR 26.3-32.9) mmHg vs. 35.2 (IQR 31.0-38.0) mmHg, p = 0.023) than those without. CONCLUSIONS: An increase in GEJ CSA, pressure, and DI, and a decrease in GEJ length can be expected during robotic sleeve gastrectomy. Patients with new or worsening post-sleeve GERD symptoms have higher post-sleeve DI and lower post-sleeve LES pressure than their asymptomatic counterparts.

Long-term potassium-competitive acid blockers administration causes microbiota changes in rats.

BACKGROUND: Vonoprazan is a new potassium-competitive acid blocker (P-CAB) that was recently approved by the FDA. It is associated with a fast onset of action and a longer acid inhibition time. Vonoprazan-containing therapy for helicobacter pylori eradication is highly effective and several studies have demonstrated that a vonoprazan-antibiotic regimen affects gut microbiota. However, the impact of vonoprazan alone on gut microbiota is still unclear.Please check and confirm the authors (Maria Cristina Riascos, Hala Al Asadi) given name and family name are correct. Also, kindly confirm the details in the metadata are correct.Yes they are correct.  METHODS: We conducted a prospective randomized 12-week experimental trial with 18 Wistar rats. Rats were randomly assigned to one of 3 groups: (1) drinking water as negative control group, (2) oral vonoprazan (4 mg/kg) for 12 weeks, and (3) oral vonoprazan (4 mg/kg) for 4 weeks, followed by 8 weeks off vonoprazan. To investigate gut microbiota, we carried out a metagenomic shotgun sequencing of fecal samples at week 0 and week 12.Please confirm the inserted city and country name is correct for affiliation 2.Yes it's correct. RESULTS: For alpha diversity metrics at week 12, both long and short vonoprazan groups had lower Pielou's evenness index than the control group (p = 0.019); however, observed operational taxonomic units (p = 0.332) and Shannon's diversity index (p = 0.070) were not statistically different between groups. Beta diversity was significantly different in the three groups, using Bray-Curtis (p = 0.003) and Jaccard distances (p = 0.002). At week 12, differences in relative abundance were observed at all levels. At phylum level, short vonoprazan group had less of Actinobacteria (log fold change = - 1.88, adjusted p-value = 0.048) and Verrucomicrobia (lfc = - 1.76, p = 0.009).Please check and confirm that the author (Ileana Miranda) and their respective affiliation 3 details have been correctly identified and amend if necessary.Yes it's correct. At the genus level, long vonoprazan group had more Bacteroidales (lfc = 5.01, p = 0.021) and Prevotella (lfc = 7.79, p = 0.001). At family level, long vonoprazan group had more Lactobacillaceae (lfc = 0.97, p = 0.001), Prevotellaceae (lfc = 8.01, p < 0.001), and less Erysipelotrichaceae (lfc = - 2.9, p = 0.029). CONCLUSION: This study provides evidence that vonoprazan impacts the gut microbiota and permits a precise delineation of the composition and relative abundance of the bacteria at all different taxonomic levels.

Gastric development of pancreatic acinar cell metaplasia after Vonoprazan therapy in rats.

BACKGROUND: Vonoprazan is a new acid-suppressing drug that received FDA approval in 2022. It reversibly inhibits gastric acid secretion by competing with the potassium ions on the luminal surface of the parietal cells (potassium-competitive acid blockers or P-CABs). Vonoprazan has been on the market for a short time and there are many clinical trials to support its clinical application. However, medical experience and comprehensive clinical data is still limited, especially on how and if, gastric histology is altered due to therapy. METHODS: A 12-week experiment trial with 30 Wistar rats was to assess the presence of gastrointestinal morphologic abnormalities upon administration of omeprazole and vonoprazan. At six weeks of age, rats were randomly assigned to one of 5 groups: (1) saline as negative control group, (2) oral omeprazole (40 mg/kg), as positive control group, (3) oral omeprazole (40 mg/kg) for 4 weeks, proceeded by 8 weeks off omeprazole, (4) oral vonoprazan (4 mg/kg), as positive control group, and (5) oral vonoprazan (4 mg/kg) for 4 weeks, proceeded by 8 weeks off vonoprazan. RESULTS: We identified non-inflammatory alterations characterized by parietal (oxyntic) cell loss and chief (zymogen) cell hyperplasia and replacement by pancreatic acinar cell metaplasia (PACM). No significant abnormalities were identified in any other tissues in the hepatobiliary and gastrointestinal tracts. CONCLUSION: PACM has been reported in gastric mucosa, at the esophagogastric junction, at the distal esophagus, and in Barrett esophagus. However, the pathogenesis of this entity is still unclear. Whereas some authors have suggested that PACM is an acquired process others have raised the possibility of PACM being congenital in nature. Our results suggest that the duration of vonoprazan administration at a dose of 4 mg/kg plays an important role in the development of PACM.

Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).

Kappa and beta-casein alleles in dairy zebu cattle.

The kappa (CSN3) and beta-casein (CSN2) genes are intensively genotyped in dairy cattle for selection purposes. This information is also generated and disseminated for Zebu breeds adapted to tropical climates. The objective of this work was to gather information on the genotypes for the CSN3 and CSN2 genes in three breeds (Gyr, Guzerat and Sindhi), and to verify the genotypic frequencies in the populations. The genotype AA and allele A frequencies are high for the CSN3 gene, without changes in values over the years, possibly indicating a small gene participation in traits under selection. In addition, the A2A2 frequencies are high for the CSN2 gene (<∼0.80). It is recommended to verify the association and contribution of CSN3 genotypes in productive traits for these breeds. The potential of A2 milk production by these genetic groups is also confirmed.

CAR T Cell Therapy: A Versatile Living Drug.

After seeing a dramatic increase in the development and use of immunotherapy and precision medicine over the past few decades, oncological care now embraces the start of the adoptive cell therapy (ACT) era. This impulse towards a new treatment paradigm has been led by chimeric antigen receptor (CAR) T cells, the only type of ACT medicinal product to be commercialized so far. Brought about by an ever-growing understanding of cellular engineering, CAR T cells are T lymphocytes genetically modified with an appropriate DNA construct, which endows them with expression of a CAR, a fusion protein between a ligand-specific recognition domain, often an antibody-like structure, and the activating signaling domain of the T cell receptor. Through this genetic enhancement, CAR T cells are engineered from a cancer patient's own lymphocytes to better target and kill their cancer cells, and the current amassed data on clinical outcomes point to a stream of bright developments in the near future. Herein, from concept design and present-day manufacturing techniques to pressing hurdles and bright discoveries around the corner, we review and thoroughly describe the state of the art in CAR T cell therapy.

Long-Term Symptoms among COVID-19 Survivors in Prospective Cohort Study, Brazil.

We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.

Diphyodont tooth replacement of Brasilodon-A Late Triassic eucynodont that challenges the time of origin of mammals.

Two sets of teeth (diphyodonty) characterise extant mammals but not reptiles, as they generate many replacement sets (polyphyodonty). The transition in long-extinct species from many sets to only two has to date only been reported in Jurassic eucynodonts. Specimens of the Late Triassic brasilodontid eucynodont Brasilodon have provided anatomical and histological data from three lower jaws of different growth stages. These reveal ordered and timed replacement of deciduous by adult teeth. Therefore, this diphyodont dentition, as contemporary of the oldest known dinosaurs, shows that Brasilodon falls within a range of wide variations of typically mammalian, diphyodont dental patterns. Importantly, these three lower jaws represent distinct ontogenetic stages that reveal classic features for timed control of replacement, by the generation of only one replacement set of teeth. This data shows that the primary premolars reveal a temporal replacement pattern, importantly from directly below each tooth, by controlled regulation of tooth resorption and regeneration. The complexity of the adult prismatic enamel structure with a conspicuous intra-structural Schmelzmuster array suggests that, as in the case of extant mammals, this extinct species would have probably sustained higher metabolic rates than reptiles. Furthermore, in modern mammals, diphyodonty and prismatic enamel are inextricably linked, anatomically and physiologically, to a set of other traits including placentation, endothermy, fur, lactation and even parental care. Our analysis of the osteodental anatomy of Brasilodon pushes back the origin of diphyodonty and consequently, its related biological traits to the Norian (225.42 ± 0.37 myr), and around 25 myr after the End-Permian mass extinction event.

Neutrophils and schistosomiasis: a missing piece in pathology.

Schistosomiasis is a chronic human parasitic disease that causes serious health problems worldwide. The disease-associated liver pathology is one of the hallmarks of infections by Schistosoma mansoni and Schistosoma japonicum, and is accountable for the debilitating condition found in infected patients. In the past few years, investigative studies have highlighted the key role played by neutrophils and the influence of inflammasome signalling pathway in different pathological conditions. However, it is noteworthy that the study of inflammasome activation in neutrophils has been overlooked by reports concerning macrophages and monocytes. This interplay between neutrophils and inflammasomes is much more poorly investigated during schistosomiasis. Herein, we reviewed the role of neutrophils during schistosomiasis and addressed the potential connection between these cells and inflammasome activation in this context.

Association of breakfast skipping with cardiovascular outcomes and cardiometabolic risk factors: an updated review of clinical evidence.

"Eat breakfast like a king, lunch like a prince and dinner like a pauper" (Adelle Davis, 1904-1974) is a concept that appears to align with some contemporary evidence concerning the appropriate proportioning of daily meals. At the same time, with the popular and scientific dissemination of the concepts of intermittent fasting and time-restricted feeding, well-controlled clinical trials have emerged showing the safety or even possible benefits of skipping breakfast. In this comprehensive literature review, we discuss recent evidence regarding breakfast intake, cardiovascular outcomes and cardiovascular risk markers. Overall, breakfast omission appears to be associated with a higher risk for atherosclerotic and adverse cardiovascular outcomes. However, caution should be employed when deciphering these data as many complex, unmeasured confounders may have contributed. Unfortunately, long-term randomized, clinical trials with detailed dietary control that have assessed clinical outcomes are sparse. Notwithstanding the observational findings, current trials conducted so far-albeit apparently smaller number-have shown that breakfast addition in subjects who do not habitually consume this meal may increase body weight, particularly fat mass, through caloric excess, whereas skipping breakfast may be a feasible strategy for some people aiming for calorie restriction. To date, definitive benefits of breakfast omission or consumption are not supported by the best evidence-based research, and the question of whether skipping breakfast per se is causally associated with cardiovascular outcomes remains unresolved.