3D Models as a Source for Neuroanatomy Education: A Stepwise White Matter Dissection Using 3D Images and Photogrammetry Scans.

White matter dissection (WMD) involves isolating bundles of myelinated axons in the brain and serves to gain insights into brain function and neural mechanisms underlying neurological disorders. While effective, cadaveric brain dissections pose certain challenges mainly due to availability of resources. Technological advancements, such as photogrammetry, have the potential to overcome these limitations by creating detailed three-dimensional (3D) models for immersive learning experiences in neuroanatomy. This study aimed to provide a detailed step-by-step WMD captured using two-dimensional (2D) images and 3D models (via photogrammetry) to serve as a comprehensive guide for studying white matter tracts of the brain. One formalin-fixed brain specimen was utilized to perform the WMD. The brain was divided in a sagittal plane and both cerebral hemispheres were stored in a freezer at -20 °C for 10 days, then thawed under running water at room temperature. Micro-instruments under an operating microscope were used to perform a systematic lateral-to-medial and medial-to-lateral dissection, while 2D images were captured and 3D models were created through photogrammetry during each stage of the dissection. Dissection was performed with comprehensive examination of the location, main landmarks, connections, and functions of the white matter tracts of the brain. Furthermore, high-quality 3D models of the dissections were created and housed on SketchFab®, allowing for accessible and free of charge viewing for educational and research purposes. Our comprehensive dissection and 3D models have the potential to increase understanding of the intricate white matter anatomy and could provide an accessible platform for the teaching of neuroanatomy.

Clinical and thermographic evaluation after lower third molar extractions and the application of different photobiomodulation protocols: double-blind randomised clinical trial.

OBJECTIVES: to compare the parameters of pain, oedema, temperature, and soft tissue closure in dental sockets that received two different photobiomodulation (PBM) protocols following extractions. MATERIALS AND METHODS: Thirty-one participants had their teeth 38 and 48 extracted. Subsequently, one of the dental sockets received PBM at a wavelength (WL) of 808 nanometers (808 group- nm) and the other dental socket received the PBM at WLs of 808 nm and 660 nm, simultaneously (808 + 660 group). The PBM was applied immediately after the surgical procedure and on the 3rd and 7th days. RESULTS: The mean of Visual Analogue Scale (VAS) values for pain were 1.45 for the 3rd day and 0.52 for the 7th day in the 808 + 660 and 808 group, respectively. The mean the pogonion-tragus measurement, used to assess facial oedema on the 3rd day, was 15.38 cm (range 13.5-17.5) in the 808 + 660 group and 15.48 cm (range 14.0-17.5) in the 808 group. The mean facial temperatures in the 808 + 660 group were 34.9 degrees Celsius (ºC) (range 33.5-36.4) on the 3rd day and 35 ºC (range 33.4-36.4) on the 7th day. In the 808 group, the mean temperatures were 34.9 ºC (range 33.9-36.2) on the 3rd day and 34.9 ºC (33.7-36.2) on the 7th day. Regarding the dimensions of the dental socket, the mean were similar for both groups. Significant differences between the groups were only observed in the pain parameter and only on the 7th day, being greater for the 808 + 660 group (p = 0.031). CONCLUSIONS: The association of the 660 nm with 808 nm, and the increase in energy did not showed more benefits in pain reduction oedema, or acceleration of the closure of the soft tissues of the dental sockets of lower third molars, in the protocols used here. CLINICAL RELEVANCE: There is no need to combine lasers at wavelengths of 660 and 808 nm to reduce oedema, pain and repair of soft tissues after extraction of lower third molars. CLINICAL TRIAL REGISTRATION: This trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the following code: RBR-66pyrh8, on 29th December, 2022.

Explaining Bounding Boxes in Deep Object Detectors Using Post Hoc Methods for Autonomous Driving Systems.

Deep learning has rapidly increased in popularity, leading to the development of perception solutions for autonomous driving. The latter field leverages techniques developed for computer vision in other domains for accomplishing perception tasks such as object detection. However, the black-box nature of deep neural models and the complexity of the autonomous driving context motivates the study of explainability in these models that perform perception tasks. Moreover, this work explores explainable AI techniques for the object detection task in the context of autonomous driving. An extensive and detailed comparison is carried out between gradient-based and perturbation-based methods (e.g., D-RISE). Moreover, several experimental setups are used with different backbone architectures and different datasets to observe the influence of these aspects in the explanations. All the techniques explored consist of saliency methods, making their interpretation and evaluation primarily visual. Nevertheless, numerical assessment methods are also used. Overall, D-RISE and guided backpropagation obtain more localized explanations. However, D-RISE highlights more meaningful regions, providing more human-understandable explanations. To the best of our knowledge, this is the first approach to obtaining explanations focusing on the regression of the bounding box coordinates.

Age-Related Changes in Clinical and Analytical Variables in Chronic Hemodialyzed Patients.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: -0.407, 0.272, -0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

Effect of digestible protein on intermediate metabolism, hepatic enzyme activities, energy reserves, and growth performance of pacu (Piaractus mesopotamicus) in the finishing growth phase.

This study investigated the effect of different levels of digestible protein (DP) on blood metabolites, hepatic enzyme activity of glycolysis and amino acid metabolism, energy reserves, and the production characteristics of pacu (Piaractus mesopotamicus) during the finishing growth phase. Six semi purified and isoenergetic diets, containing 16.3, 20.1, 23.8, 27.2, 31.5, and 34.8% of balanced DP, provided with essential amino acid balance, were hand-fed to pacu (1100.0 ± 10.3 g, initial weight) three times daily for 7 weeks. The experiment consisted of six treatments, with three randomly arranged replicates (tanks) per treatment. The data obtained from this experiment were analyzed by one-way analysis of variance (ANOVA), and significant differences (p < 0.05) between treatments were determined using Tukey's test. Blood metabolites, except serum ammonia and the hepatic enzymes activities of glycolysis and amino acid metabolism, except hexokinase activity were affected (p < 0.05) by balanced DP. The energy reserve indices, except hepatic total lipid content, were also found associated (p < 0.05) with balanced DP. The test diets significantly (p < 0.05) affected growth performance parameters. Higher dietary proteins led to a greater energy uptake by fish from the protein in feed. Overall, fish fed the intermediate level (23.8%) of balanced DP with digestible energy of 17.95 MJ kg-1 showed better production traits and physio-biochemical health markers. This information could help nutritionists and farmers to develop nutritionally balanced and economically and environmentally sustainable aquafeed for promoting healthy and sustainable production of pacu in intensive culture systems.

Non-invasive cardiovascular magnetic resonance assessment of pressure recovery distance after aortic valve stenosis.

BACKGROUND: Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40-50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. METHODS: We developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. RESULTS: In-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40-50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. CONCLUSION: The non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.

Material jetting of carbon nano onions for printed electronics.

As an additive manufacturing process, material jetting techniques allow to selectively deposit droplets of materials in liquid or powder form through a small-diameter aperture, such as a nozzle of a print head. For the fabrication of printed electronics, a variety of inks and dispersions of functional materials can be deposited by drop-on-demand printing on rigid and flexible substrates. In this work, zero-dimensional multi-layer shell-structured fullerene material, also known as carbon nano-onion (CNO) or onion-like carbon, is printed on polyethylene terephthalate substrates using drop-on-demand inkjet printing. CNOs are produced using a low-cost flame synthesis technique and characterized by electron microscopy, Raman, x-ray photoelectron spectroscopy, and specific surface area and pore size measurements. The produced CNO material has an average diameter of ∼33 nm, pore diameter in the range ∼2-40 nm and a specific surface area of 160 m2.g-1. The CNO dispersions in ethanol have a reduced viscosity (∼1.2 mPa.s) and are compatible with commercial piezoelectric inkjet heads. The jetting parameters are optimized to avoid satellite drops and to obtain a reduced drop volume (52 pL), resulting in optimal resolution (220µm) and line continuity. A multi-step process is implemented without inter-layer curing and a fine control over the CNO layer thickness is achieved (∼180 nm thick layer after 10 printing passes). The printed CNO structures show an electrical resistivity of ∼600 Ω.m, a high negative temperature coefficient of resistance (-4.35 × 10-2°C-1) and a marked dependency on relative humidity (-1.29 × 10-2RH%-1). The high sensitivity to temperature and humidity, combined to the large specific area of the CNOs, make this material and the corresponding ink a viable prospect for inkjet-printed technologies, such as environmental and gas sensors.

Multitargeting approaches to cognitive impairment: Synthesis of aryl-alkylpiperazines and assessment at cholinesterases, histamine H3 and dopamine D3 receptors.

Multitargeting ligands on enzymes and receptors may generate a profile for a potential treatment of cognitive impairment. Considering this, a set of 21 substituted aryl-alkyl-piperazines were designed, prepared and tested for their binding affinities at histamine H3 and dopamine D3 receptors (H3R and D3R, respectively) as well as acetyl- and butyrylcholinesterases (AChE/BChE) as potentially synergistic profile. Initial screening of the compounds at H3R and D3R was done at 1 or 10 µM and 100 µM at AChE and BChE assays. The most promising compounds were then evaluated in full concentration-response curves to estimate the Ki and IC50 values. Results showed that several compounds were ligands at H3R (n = 10), D3R (n = 6), AChE (n = 3), and BChE (n = 9). Compounds LINS05006 (Ki H3R 2.8 µM; D3R 0.7 µM; IC50 BChE 26.3 µM) and LINS05015 (Ki H3R 1.1 µM; D3R 3.1 µM; IC50 AChE 97.8 µM; BChE 43.7 µM) are highlighted since presented affinity in three different. These results suggest that methylpiperazine moiety led to balanced activity at all three classes of targets, and longer linker provided the best affinities. These compounds presented high ligand efficiency values (LE > 0.3) and may have adequate pharmacokinetic profile as suggested by calculated physicochemical properties.

Is there a time window for MRI in Wernicke encephalopathy - a decade of experience from a tertiary hospital.

OBJECTIVE: Wernicke encephalopathy (WE) is a neuropsychiatric syndrome caused by thiamine deficiency. Despite its low sensitivity, brain magnetic resonance imaging (MRI) is the most useful diagnostic technique. Our aim was to investigate whether the timing of the imaging study, and thiamine replacement can influence brain MRI findings in these patients. METHODS: Retrospective observational study of hospitalized patients between January/2008 and December/2020 with a clinical diagnosis of WE. Data from clinical presentation, diagnostic features, therapeutic approach, and outcomes were collected. RESULTS: We identified 41 patients (55 ± 13.3 years) with WE. Brain MRI was performed in 36 patients, and one third had T2/FLAIR hyperintensities suggestive of WE. We found an association between a history of poor diet and periventricular hyperintensities (p = 0.023), especially on the ventral surface of the thalamus and the periaqueductal region. It was found that the odds of having a typical imaging of WE decreased by 5.3% for each additional unit (100 mg) of thiamine administered (p = 0.046) (95% CI [0.89, 0.99]). On the other hand, the number of days from clinical presentation was not found to be a viable predictor (p = 0.254) (95% CI [0.88, 1.03]) Recovery was positively correlated with the total dose of thiamine received until discharge (p = 0.020). CONCLUSIONS: MRI hyperintensities seem to be dependent on the timing of thiamine correction and, particularly, on the thiamine dosage prescribed at admission. Nevertheless, thiamine replacement should not be delayed, as its timely prescription is associated with a better prognosis at discharge.

Peritoneal Dialysis Exit-Site Care Protocols in Portugal and Its Association with Catheter-Related Infections.

INTRODUCTION: Exit-site infection (ESi) prevention is a key factor in lowering the risk of peritonitis. This study aimed to evaluate the associations between exit-site (ES) care protocols and the annual incidence rates of ESi and peritonitis in Portugal. METHODS: We performed a national survey using two questionnaires: one about the incidence of catheter-related infections and the other characterizing patients' education and ES care protocols. RESULTS: In 2017 and 2018, 14 Portuguese units followed 764 and 689 patients. ESi incidence rate was 0.41 episodes/year, and the peritonitis incidence rate was 0.37. All units monitor catheter-related infections on a yearly basis, use antibiotic prophylaxis at the time of catheter placement, and treat nasal carriage of S. aureus, although with different approaches. Screening for nasal carriage of S. aureus is performed by 12 units, and daily topical antibiotic cream is recommended by 6 out of 14 of the units. We did not find statistical differences in ESi/peritonitis, comparing these practices. The rate of ESis was lower with nonocclusive dressing immediately after catheter insertion, bathing without ES dressing, with the use of colostomy bags in beach baths and was higher with the use of bath sponge. The peritonitis rate was lower with bathing without ES dressing and if shaving of the external cuff was performed in the presence of chronic ESi. CONCLUSIONS: We found potential proceedings associated with ESi and peritonitis. A regular national audit of peritoneal dialysis units is an important tool for clarifying the best procedures for reduction of catheter-related infections.

First report of root-knot nematode, Meloidogyne javaniva, infecting Stachys byzantina on São Paulo, Brazil.

Stachys byzantina belongs to the Labiatae and is known by the names "peixinho-da-horta" (Brazil) and "lamb's ear" (USA). Its importance is associated with its medicinal properties (Bahadori et al. 2020) and nutritional aspects (Milião et al. 2022). Root-knot nematodes cause severe damage to plants and suppress production. In January 2021, plants of S. byzantina in the municipality of Jaboticabal (21°14'38.7"S, 48°17'10.6"W) showed symptoms of reduced growth, yellowed leaves and the presence of galls in the roots. Initially, samples of roots from a S. byzantina were analyzed at the Nematology Laboratory (LabNema/UNESP), Jaboticabal, Brazil, estimating 20,000 eggs and juveniles of Meloidogyne sp. in 10 g of roots. To confirm the host ability of the species, a pathogenicity test was performed using Koch's postulate. For this purpose, the test was conducted in a greenhouse where 3,000 eggs and second-stage juveniles (J2) were inoculated onto three plants (n=3) of S. byzantina. After 90 days, the inoculated plants showed the same symptoms as those observed in the field. No symptom or nematode was detected in the uninoculated plant (control). Nematodes were extracted from the roots of inoculated plants and quantified. The perineal pattern of females (n=10) (Netscher and Taylor, 1974) and the labial region of males (n=10) (Eisenback and Hirschmann, 1981) were analyzed and compared with the morphological characteristics of the original description of the species (Chitwood, 1949). For analysis based on esterase isozyme phenotype, the α-method of Esbenshade and Triantaphyllou (1990) was used, and females (n=7) were examined. To confirm identification, whole genomic DNA from an adult female (n=1) was extracted using the Qiagen DNeasy® Blood & Tissue Kit and this sample was used for both genetic sequencing and the sequence-characterized amplified region techniques (SCAR). PCR amplifications were performed for the 18s rRNA gene using primers 988F and 1912R from Holterman et al (2006). Our sequence was deposited in GenBank (NCBI) under the identifier OP422209. Finally, species-specific SCAR primers (Fjav/Rjav, Me-F/Me-R, and Finc-F/Finc-R) designed by Zijlstra (2000) were used to identify Meloidogyne spp. Koch's postulate analysis yielded the following results: (n=1) 9,280 eggs and J2 (Reproduction factor, RF = 33.09); (n=2) 111,720 eggs and J2 (RF = 37.24); (n=3) 59,700 eggs and J2 (RF = 19.9) (RF mean = 30.08). The following characteristics were observed in the perineal region of females: Low and rounded trapezoidal dorsal arch with two distinct lateral lines clearly separating the dorsal and ventral arch regions, similar to the morphological features of the species description by Chitwood (1949). Males had a convex labial plate with a non-raised labial disk joining the submedial labia, a non-rugged labial region, the basal tubercles were usually wider than high, and a rounded tail tip (Eisenback and Hirschmann 1981). The α-esterase enzyme profile showed the J3 phenotype typical of M. javanica (Rm [×100] = 46.0, 54.5, and 58.9). The 18s rRNA sequences grouped Meloidogyne sp. with species such as M. enterolobii, M. incognita, and M. javanica. A DNA fragment of about 700 bp was amplified with Mj (Fjav/Rjav) primers, but not with Me (Me-F/Me-R) and Mi (Finc-F/Finc-R) primers, which confirmed the identification of M. javanica. Accurate identification and characterization of the occurrence of new hosts of M. javanica will allow us to determine the range and geographic distribution of the species. This is the first report on the occurrence of M. javanica on S. byzantina in Brazil. This report is important so that management strategies can be applied to prevent the spread of the pest to other areas.

Anti-Aging Potential of a Novel Ingredient Derived from Sugarcane Straw Extract (SSE).

Natural and sustainable anti-aging ingredients have gained attention from the cosmetic industry. This study evaluated the anti-aging potential of a sugarcane straw extract-based (SSE) cosmetic ingredient. First, cytotoxicity tests were assessed in keratinocytes and fibroblast cell lines, and sensitization was carried out through the direct peptide reactivity assay. Subsequently, various anti-aging properties were investigated, including inhibiting skin aging-related enzymes, promoting elastin and hyaluronic acid synthesis, and anti-pollution activity. Finally, a permeability assay using a synthetic membrane resembling skin was conducted. The results demonstrated that the SSE ingredient effectively inhibited elastase (55%), collagenase (25%), and tyrosinase (47%) while promoting hyaluronic acid production at non-cytotoxic and low-sensitizer concentrations. Moreover, it reduced the inflammatory response provoked by urban pollution, as evidenced by decreased levels of IL1-α and IL-6. However, it was observed that the phenolic compounds predominantly reached the skin's surface, indicating a limited ability to penetrate deeper layers of the skin. Therefore, it can be concluded that the SSE ingredient holds anti-aging properties, albeit with limited penetration into deeper skin layers. Further research and formulation advancements are needed to optimize the ingredient's ability to reach and exert its effects in deeper skin layers.

Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota.

Cannabidiol (CBD) and cannabigerol (CBG) are two pharmacologically active phytocannabinoids of Cannabis sativa L. Their antimicrobial activity needs further elucidation, particularly for CBG, as reports on this cannabinoid are scarce. We investigated CBD and CBG's antimicrobial potential, including their ability to inhibit the formation and cause the removal of biofilms. Our results demonstrate that both molecules present activity against planktonic bacteria and biofilms, with both cannabinoids removing mature biofilms at concentrations below the determined minimum inhibitory concentrations. We report for the first time minimum inhibitory and lethal concentrations for Pseudomonas aeruginosa and Escherichia coli (ranging from 400 to 3180 µM), as well as the ability of cannabinoids to inhibit Staphylococci adhesion to keratinocytes, with CBG demonstrating higher activity than CBD. The value of these molecules as preservative ingredients for cosmetics was also assayed, with CBG meeting the USP 51 challenge test criteria for antimicrobial effectiveness. Further, the exact formulation showed no negative impact on skin microbiota. Our results suggest that phytocannabinoids can be promising topical antimicrobial agents when searching for novel therapeutic candidates for different skin conditions. Additional research is needed to clarify phytocannabinoids' mechanisms of action, aiming to develop practical applications in dermatological use.

Microgap and bacterial microleakage during the osseointegration period: An in vitro assessment of the cover screw and healing abutment in a platform-switched implant system.

STATEMENT OF PROBLEM: Microgap and bacterial microleakage at the implant-prosthetic abutment interface are recognized concerns for implant-supported restorations, leading to inflammation of the peri-implant tissues, with deleterious consequences for crestal bone levels. However, little is known regarding the interface established between the implant and the healing abutment or cover screw placed for the osseointegration phase. PURPOSE: The purpose of this in vitro study was to characterize the implant-cover screw and implant-healing abutment interfaces of a platform-switched implant system to determine the microgap and bacterial microleakage of the system and evaluate the biological response and functionality of an interface sealing agent. MATERIAL AND METHODS: The interfacial microgaps of the implant-healing abutment and implant-cover screw interfaces were characterized by scanning electron microscopy (n=10), and bacterial microleakage was evaluated after colonization with Enterococcus faecalis in a 30-day follow-up (n=10). The sealing efficacy and irritation potential of a silicone-based sealer were determined by using the hen's egg test on chorioallantoic membrane assay. The 2-sample t test was performed to compare means between groups, and data presented with the Kaplan-Meier method were compared statistically by using the log-rank test (α=.05). RESULTS: The interfacial microgap was less than 2.5 µm for both systems. Bacterial microleakage was noted in approximately 50% of the specimens, particularly at early time points, at both the healing abutment and cover screw interfaces. The silicone-based sealer prevented bacterial leakage in the experimental setting. CONCLUSIONS: The implant-healing abutment and implant-cover screw interfaces of the tested system, despite the low microgap, allowed for bacterial microleakage after internal colonization. The use of a nonirritating silicone-based sealing agent effectively sealed the system.

Giant thoracic aorta aneurysm below an endovascular stent - An unexpected finding during linear endoscopic ultrasound.

A 50-year-old woman with a history of bicuspid aortic valve (BAV) and ascending aorta dissection was referred for endoscopic ultrasound (EUS) for suspected choledocholithiasis. Twelve years earlier she had undergone a Bentall-de Bone procedure and 7 years earlier a thoracic aorta aneurysm (TAA) was repaired with an endovascular prosthesis. EUS confirmed choledocholithiasis, however a large aneurysm (60 mm of diameter), was incidentally detected at the distal end of the aortic endoprosthesis. Computed tomography (CT) later confirmed the aneurysm, extending 4.5 cm above the renal arteries. The patient underwent a successful new endovascular repair. This rare incidental finding underscores the usefulness of a systematic approach when performing EUS, enabling the detection of significant abnormalities beyond the initial indication and allowing for early intervention in TTA patients.

Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study.

OBJECTIVE: To better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH. PATIENTS AND METHODS: Physician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model. RESULTS: Overall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12-1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68-11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19-2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30-7.63; p=0.010) times higher for those unable to work due to NASH. CONCLUSIONS: Disease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH.

Piperazine amides with desirable solubility, physicochemical and drug-like properties: Synthesis and evaluation of the anti-Trypanosoma cruzi activity.

The absence of effective chronic treatment, expansion to non-endemic countries and the significant burden in public health have stimulated the search for novel therapeutic options to treat Chagas disease, a protozoan disease caused by Trypanosoma cruzi. Despite current efforts, no new drug candidates were approved in clinical trials in the past five decades. Considering this, our group has focused on the expansion of a series (LINS03) with low micromolar activity against amastigotes, considering the optimization of pharmacokinetic properties through increasing drug-likeness and solubility. In this work, we report a new set of 13 compounds with modifications in both the arylpiperazine and the aromatic region linked by an amide group. Five analogues showed activity against intracellular amastigotes (IC50 17.8 to 35.9 µM) and no relevant cytotoxicity to mammalian cells (CC50 > 200 µM). Principal component analysis (PCA) was performed to identify structural features associated to improved activity. The data revealed that polarity, hydrogen bonding ability and flexibility were key properties that influenced the antiparasitic activity. In silico drug-likeness assessments indicated that compounds with the 4-methoxycinammyl (especially compound 2b) had the most prominent balance between properties and activity in the series, as confirmed by SAR analysis.

Acute and chronic effects of physical exercise on IgA and IgG levels and susceptibility to upper respiratory tract infections: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed at evaluating acute and chronic effects of physical exercise on IgA and IgG levels, as well as its relationship with the susceptibility to develop upper respiratory tract infections (URTI). This systematic review and meta-analysis was conducted and reported in accordance with PRISMA statement. A systematic search of PubMed, Web of Science, and EMBASE was performed in July 2020. This systematic review and meta-analysis included studies in which participants performed acute exercise or chronic physical training and were subjected to analyses of URTI incidence and concentrations of IgA and IgG. The selected studies for systematic review were divided into the following three groups: (I) trials that evaluated the effects of acute exercise in sedentary subjects, (II) trials that evaluated the effects of acute exercise in athletes/trained individuals, and (III) trials that evaluated the effects of chronic physical training on the incidence of URTI, as well as on the levels of IgA and IgG. Acute exercise increases the IgA levels in trained subjects but does not affect its levels in untrained subjects. Such increase in IgA levels induced by acute exercise is greater in trained individual that performed ultramarathon. On the other hand, chronic physical training reduces IgA levels in both trained and untrained subjects, does not change IgA levels in non-military subjects, besides from not affecting IgG levels. The present systematic review and meta-analysis indicates that acute exercise positively influences IgA levels in trained individuals, being this effect pronounced when a strenuous exercise such as ultramarathon is executed. Chronic physical training, in turn, does not affect IgG levels.

Adherence to and persistence with antidiabetic medications and associations with clinical and economic outcomes in people with type 2 diabetes mellitus: A systematic literature review.

We designed a systematic literature review to identify available evidence on adherence to and persistence with antidiabetic medication in people with type 2 diabetes (T2D). Electronic screening and congress searches identified real-world noninterventional studies (published between 2010 and October 2020) reporting estimates of adherence to and persistence with antidiabetic medication in adults with T2D, and associations with glycaemic control, microvascular and/or macrovascular complications, hospitalizations and healthcare costs. Ninety-two relevant studies were identified, the majority of which were retrospective and reported US data. The proportions of patients considered adherent (median [range] 51.2% [9.4%-84.3%]) or persistent (median [range] 47.7% [16.9%-94.0%]) varied widely across studies. Multiple studies reported an association between greater adherence/persistence and greater reductions in glycated haemoglobin levels. Better adherence/persistence was associated with fewer microvascular and/or macrovascular outcomes, although there was little consistency across studies in terms of which outcomes were improved. More adherent and more persistent patients were typically less likely to be hospitalized or to have emergency department visits/admissions and spent fewer days in hospital annually than less adherent/persistent patients. Greater adherence and persistence were generally associated with lower hospitalization costs, higher pharmacy costs and lower or budget-neutral total healthcare costs compared with lower adherence/persistence. In conclusion, better adherence and persistence in people with T2D is associated with lower rates of microvascular and/or macrovascular outcomes and inpatient hospitalization, and lower or budget-neutral total healthcare expenditure. Education and treatment strategies to address suboptimal adherence and persistence are needed to improve clinical and economic outcomes.

Histamine research advancements in the second year of the COVID-19 pandemic: report of the European Histamine Research Society (EHRS).

In the light of cancellation of the 50th Annual Meeting of the European Histamine Research Society (EHRS) due to continuing challenges and restrictions imposed by the coronavirus disease 2019 (COVID-19) outbreak, the EHRS Council decided to organize a series of online events spread in 2021 to allow dissemination of histamine research progress and advancement among the Society members and beyond. This report summarizes the outcomes of the EHRS Council initiative that comprised the organization of four webinars, each focusing on a highly relevant histamine research scientific area. These included insights into novel therapeutic targets related to the histaminergic system in the eye, histamine intolerance, and the role of histamine and the histaminergic system in the regulation of the nervous system, as well as an update on studies leading to the development of novel methods for histamine detection. The outcome of this series of virtual events conformed that histamine research continued to develop despite the pandemic, and we witnessed stimulating advancements in 2021. Importantly, the EHRS Council brought histaminologists together in this unprecedented time.