Binocular vision parameters and visual performance in bilateral keratoconus corrected with spectacles versus rigid gas-permeable contact lenses / Parámetros de visión binocular y rendimiento visual en queratocono bilateral corregido con gafas versus lentes de contacto rígidos permeables al gas

Purpose: To analyze binocular vision of individuals aged 18 to 35 years diagnosed with keratoconus, utilizing spectacles and rigid gas-permeable (RGP) contact lenses. Research was led by the Universidad Autónoma de Aguascalientes, México and Fundación Universitaria del Área Andina Pereira, Colombia. Methods: A single center, prospective non-randomized, comparative, interventional, open-label study, in which the differences in binocular vision performance with both spectacles and RGP contact lenses was carried out from December 2018 to December 2019. Sampling was performed according to consecutive cases with keratoconus that met the inclusion criteria until the proposed sample size was reached. Results: Rigid gas-permeable (RGP) contact lenses notably enhanced distance and near visual acuity in keratoconus patients compared to spectacles. Visual alignment analysis shows exophoria at both distances and is slightly higher with RGP contact lenses. The difference was statistically significant (p<0.05), with 82.5 % presenting compensated phoria with spectacles and pnly 42.50% with RGP contact lenses. Stereoscopic vision improved while wearing RGP contact lenses (42.59 %), although accommodation and accommodative flexibility remained within normal ranges. Conclusions: Patients with keratoconus fitted with RGP contact lenses have improved binocular vision skills such as visual acuity, stereopsis, and accommodative flexibility. However, even when the vergence and motor system is decompensated with respect to normal ranges, the range between break and recovery points for both fusional reserves and the near point of convergence (NPC) improves with the use of RGP contact lenses, giving indications of an adaptive condition of the motor system from the medium to the long term.(AU)

Comparison of the efficacy of cisplatin and carboplatin in combination with etoposide in firstline treatment of extensive-stage small cell lung cancer in real-world practice in the Czech Republic - a retrospective analysis of patients from the LUCAS project.

BACKGROUND: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a poor prognosis. The standard palliative treatment for four decades has been chemotherapy as a combination of etoposide with carboplatin or cisplatin, and in recent years, immunotherapy in addition. AIMS: To determine whether there is a difference in the efficacy of palliative chemotherapy as cisplatin or carboplatin in combination with etoposide in patients with ES-SCLC in real-world practice in the Czech Republic. METHODS: This was a retrospective analysis of a cohort of 348 patients from the LUCAS project with ES-SCLC. 79 were treated with etoposide plus cisplatin and 265 were treated with etoposide plus carboplatin. Kaplan-Meier curves and the Cox regression model were used for analysis. RESULTS: No statistically significant difference in median overall survival (mOS) or median progression free survival (mPFS) was found between groups or between patients grouped according to age and performance status (PS) in mOS. The Cox regression result was similar. CONCLUSION: This study shows that cisplatin and carboplatin do not differ in efficacy in a given indication, thus when choosing a treatment, the physician should consider the expected toxicity in a particular patient, assessing the patient's general condition and comorbidities.

Molecular Dynamic Simulations for Biopolymers with Biomedical Applications.

Computational modeling (CM) is a versatile scientific methodology used to examine the properties and behavior of complex systems, such as polymeric materials for biomedical bioengineering. CM has emerged as a primary tool for predicting, setting up, and interpreting experimental results. Integrating in silico and in vitro experiments accelerates scientific advancements, yielding quicker results at a reduced cost. While CM is a mature discipline, its use in biomedical engineering for biopolymer materials has only recently gained prominence. In biopolymer biomedical engineering, CM focuses on three key research areas: (A) Computer-aided design (CAD/CAM) utilizes specialized software to design and model biopolymers for various biomedical applications. This technology allows researchers to create precise three-dimensional models of biopolymers, taking into account their chemical, structural, and functional properties. These models can be used to enhance the structure of biopolymers and improve their effectiveness in specific medical applications. (B) Finite element analysis, a computational technique used to analyze and solve problems in engineering and physics. This approach divides the physical domain into small finite elements with simple geometric shapes. This computational technique enables the study and understanding of the mechanical and structural behavior of biopolymers in biomedical environments. (C) Molecular dynamics (MD) simulations involve using advanced computational techniques to study the behavior of biopolymers at the molecular and atomic levels. These simulations are fundamental for better understanding biological processes at the molecular level. Studying the wide-ranging uses of MD simulations in biopolymers involves examining the structural, functional, and evolutionary aspects of biomolecular systems over time. MD simulations solve Newton's equations of motion for all-atom systems, producing spatial trajectories for each atom. This provides valuable insights into properties such as water absorption on biopolymer surfaces and interactions with solid surfaces, which are crucial for assessing biomaterials. This review provides a comprehensive overview of the various applications of MD simulations in biopolymers. Additionally, it highlights the flexibility, robustness, and synergistic relationship between in silico and experimental techniques.

Combination of error-prone PCR (epPCR) and Circular Polymerase Extension Cloning (CPEC) for improving the coverage of random mutagenesis libraries.

Random mutagenesis, such as error-prone PCR (epPCR), is a technique capable of generating a wide variety of a single gene. However, epPCR can produce a large number of mutated gene variants, posing a challenge in ligating these mutated PCR products into plasmid vectors. Typically, the primers for mutagenic PCRs incorporate artificial restriction enzyme sites compatible with chosen plasmids. Products are cleaved and ligated to linearized plasmids, then recircularized by DNA ligase. However, this cut-and-paste method known as ligation-dependent process cloning (LDCP), has limited efficiency, as the loss of potential mutants is inevitable leading to a significant reduction in the library's breadth. An alternative to LDCP is the circular polymerase extension cloning (CPEC) method. This technique involves a reaction where a high-fidelity DNA polymerase extends the overlapping regions between the insert and vector, forming a circular molecule. In this study, our objective was to compare the traditional cut-and-paste enzymatic method with CPEC in producing a variant library from the gene encoding the red fluorescent protein (DsRed2) obtained by epPCR. Our findings suggest that CPEC can accelerate the cloning process in gene library generation, enabling the acquisition of a greater number of gene variants compared to methods reliant on restriction enzymes.

Interesting Cytokine Profile Caused by Clinical Strains of Pseudomonas aeruginosa MDR Carrying the exoU Gene.

Pseudomonas aeruginosa is an opportunistic pathogen in HAIs with two facets: the most studied is the high rate of antimicrobial resistance, and the less explored is the long list of virulence factors it possesses. This study aimed to characterize the virulence genes carried by strains as well as the profile of cytokines related to inflammation, according to the resistance profile presented. This study aims to identify the virulence factors associated with MDR strains, particularly those resistant to carbapenems, and assess whether there is a cytokine profile that correlates with these characteristics. As methodology species were identified by classical microbiological techniques and confirmed by molecular biology, resistance levels were determined by the minimum inhibitory concentration and identification of MDR strains. Virulence factor genotyping was performed using PCR. In addition, biofilm production was assessed using crystal violet staining. Finally, the strains were cocultured with PBMC, and cell survival and the cytokines IL-1ß, IL-6, IL-10, IL-8, and TNF-α were quantified using flow cytometry. Bacteremia and nosocomial pneumonia in adults are the most frequent types of infection. In the toxigenic aspect, genes corresponding to the type III secretion system were present in at least 50% of cases. In addition, PBMC exposed to strains of four different categories according to their resistance and toxicity showed a differential pattern of cytokine expression, a decrease in IL-10, IL-6, and IL-8, and an over-secretion of IL-1b. In conclusion, the virulence genes showed a differentiated appearance for the two most aggressive exotoxins of T3SS (exoU and exoS) in multidrug-resistant strains. Moreover, the cytokine profile displays a low expression of cytokines with anti-inflammatory and proinflammatory effects in strains carrying the exoU gene.

Favourable effect of clavulanic acid on the minimum inhibitory concentrations of cefixime and ceftibuten in ESBL-producing Escherichia coli and Klebsiella pneumoniae.

OBJECTIVES: The use of cephalosporins combined with clavulanate for the treatment of ESBL-harbouring Enterobacteriaceae has been scarcely described. We aimed to describe the effect of different concentrations of clavulanate in the MIC of cefixime and ceftibuten of ESBL-producing Escherichia coli and Klebsiella pneumoniae. METHODS: ESBL-producing E. coli and K. pneumoniae isolates were studied. Fixed concentrations of cefixime and ceftibuten (ranges of 32-0.25 and 64-0.5 ng/ml, respectively) were used. Combinations of cefixime/clavulanate and ceftibuten/clavulanate in different ratios (1:0, 1:1, 2:1, 4:1, 8:1, 16:1, 32:1) were tested. MIC were determined by broth microdilution. RESULTS: A total of 6 ESBL-producing E. coli, 6 ESBL-producing K. pneumoniae and 2 control E. coli were tested. When different quantities of clavulanate were added to cefixime and ceftibuten, greater than two-fold decreases in the MIC were observed. When testing the 1:1 cefixime/clavulanate ratio, 10/12 isolates were susceptible. When the ratios 2:1, 4:1, 8:1, and 16:1 were tested, susceptibility was noted for 9/12, 8/12, 4/12, and 5/12 isolates, respectively. Only 2/12 K. pneumoniae isolates were susceptible when the ratio 32:1 was tested. When testing ceftibuten/clavulanate, all isolates remained susceptible across all experiments. CONCLUSIONS: Clavulanic acid has a favourable effect in reducing the MIC of cefixime and ceftibuten in isolates of ESBL-producing E. coli and K. pneumoniae. Combining clavulanate with ceftibuten or cefixime could be a useful treatment strategy.

Multi-Organ Systems Involvement in COVID-19 is Associated With a Worse Prognosis.

Background: Coronavirus disease 2019 (COVID-19) has multiple organ system involvement but the association of organ system involvement with disease prognosis has not been reported. We study the association of organ systems involved with in-hospital mortality and hospital length of stay (LOS) in COVID-19. Methods: Retrospective study of 808 consecutive patients with confirmed-laboratory diagnosis of COVID-19 in a New York hospital from March 1-May 15, 2020. Results: Increased number of organs systems involved was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.11-1.66, p < 0.01) and increased LOS (B = 0.02, SE = 0.01, p < 0.05). Increased platelet count was associated with decreased odds for mortality (OR: 0.996, 95% CI: 0.994-0.998, p < 0.001). Increased white blood cell count was associated with increased odds for mortality (OR: 14.00, 95% CI: 3.41-57.38, p < 0.001). Increased creatinine and glucose were each associated with increased LOS (B = 0.11, SE = 0.04, p < 0.01, and B = 0.12, SE = 0.05, p < 0.05, respectively). Increased odds for mortality were also found in high FiO2 oxygen requirement (OR: 11.63, 95% CI: 3.90-34.75, p < 0.001) and invasive mechanical ventilation (OR: 109.93, 95% CI: 29.44-410.45, p < 0.001). Conclusion: Multiple organ systems involvement in COVID-19 is associated with worse prognosis. Clinical/laboratory values corresponding to each organ system may be used as prognostic tools in clinical settings to tailor treatments for COVID-19 patients.

Immunologic characterization of the Bm05br protein using the Rhipicephalus linnaei (Audouin, 1826) species as a tick model.

The identification and characterization of tick proteins allow us to discover new physiological targets useful for the development of tick control methods. Bm05br (Brazil Rhipicephalus microplus protein 05) is a protein with unknown function identified in the saliva of R. microplus. Rs05br (Brazil Rhipicephalus sanguineus protein 05), a protein with 99 % similarity to Bm05br, was identified in Rhipicephalus linnaei egg, larval, and nymphal stages, as well as in adult saliva. To improve the knowledge about both proteins, immunological characterization was performed, including antigenicity analysis, vaccination trials, and artificial feeding. The sequence and antigenicity analysis of Bm05br and Rs05br proteins showed that R. linnaei could serve as a tick model for cross-protection studies. The recombinant Bm05br protein was immunogenic. Anti-Bm05br antibodies recognized the homologous protein Rs05br in different stages, organs, and in the saliva of R. linnaei. Although rBm05br did not induce a protective response against infestation in R. linnaei in this study, further experiments could be developed taking into account new formulations and animal models for vaccination. These results also serve as a reference for future research on the function of these proteins in R. microplus and R. linnaei physiology, as well as other species of the genus Rhipicephalus.

Robotic-assisted cholecystectomy versus conventional laparoscopic cholecystectomy for benign gallbladder disease: a systematic review and meta-analysis.

Laparoscopic cholecystectomy (LC) is the established gold standard treatment for benign gallbladder diseases. However, robotic cholecystectomy is still controversial. Therefore, we aimed to compare intraoperative and postoperative outcomes in LC and robotic-assisted cholecystectomy (RAC) in patients with nonmalignant gallbladder conditions. PubMed, Scopus, Cochrane Library, and Web of Science were systematically searched for studies comparing RAC to LC in patients with benign gallbladder disease. Only randomized trials and non-randomized studies with propensity score matching were included. Mean differences (MDs) were computed for continuous outcomes and odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics. Statistical analysis was performed using Software R, version 4.2.3. A total of 13 studies comprising 22,440 patients were included, of whom 10,758 patients (47.94%) underwent RAC. The mean age was 48.5 years and 65.2% were female. Compared with LC, RAC significantly increased operative time (MD 12.59 min; 95% CI 5.62-19.55; p < 0.01; I2 = 79%). However, there were no significant differences between the groups in hospitalization time (MD -0.18 days; 95% CI - 0.43-0.07; p = 0.07; I2 = 89%), occurrence of intraoperative complications (OR 0.66; 95% CI 0.38-1.15; p = 0.14; I2 = 35%) and bile duct injury (OR 0.99; 95% CI 0.64, 1.55; p = 0.97; I2 = 0%). RAC was associated with an increase in operative time compared with LC without increasing hospitalization time or the incidence of intraoperative complications. These findings suggest that RAC is a safe approach to benign gallbladder disease.

Developing an Evidence-Based Ethics Education Program for Surgical Residents in Guatemala.

OBJECTIVE: This study assessed 2 modalities for teaching responsible conduct of research and human subjects protection (RCR/HSP) to surgical residents in Guatemala-an "off the shelf" online curriculum and a new in-person curriculum specific to the local context. METHODS: In 2018, 160 surgical residents in 3 large urban hospitals in Guatemala City completed 2 online programs in RCR/HSP. Residents in the intervention arm also completed 7 weeks of in-person training. Pre- and post-assessments tested awareness of key concepts with particular attention to international and Guatemalan research regulations. Group differences in matched (pre- and post-) mean scores were analyzed using t-tests. RESULTS: One hundred forty residents completed pre- and post-training assessments and were included in the analytic sample. Overall mean scores improved modestly from 52.7 to 58.7 points out of 100. Intervention-arm trainees reported greater confidence in recognizing ethical issues, understanding legal and ethical requirements for research, and identifying, reporting and avoiding scientific misconduct than control-arm trainees. CONCLUSION: Given the limited availability of RCR/HSP faculty, financial resources, and time in the surgical training schedule, the investigators recommend that academic authorities in Guatemala consider online training programs in RCR/HSP in all surgical residency programs as an affordable and scalable strategy to build ethical research skills in its surgical workforce. Investment in human resources to support in-person ethics education as a way to build self-efficacy in ethical decision-making should be considered.

Optogenetic ß cell interrogation in vivo reveals a functional hierarchy directing the Ca2+ response to glucose supported by vitamin B6.

Coordination of cellular activity through Ca2+ enables ß cells to secrete precise quantities of insulin. To explore how the Ca2+ response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual ß cells in the glucose response. By targeted ß cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca2+ dynamics. First-responder ß cells lie at the top of the hierarchy, essential for initiating the first-phase Ca2+ response. Silencing first responders impairs the Ca2+ response to glucose. Conversely, selective activation of first responders demonstrates their increased capability to raise pan-islet Ca2+ levels compared to followers. By photolabeling and transcriptionally profiling ß cells that differ in their thresholds to a glucose-stimulated Ca2+ response, we highlight vitamin B6 production as a signature pathway of first responders. We further define an evolutionarily conserved requirement for vitamin B6 in enabling the Ca2+ response to glucose in mammalian systems.

Ultrasonographic Insights into Peripheral Psoriatic Arthritis: Updates in Diagnosis and Monitoring.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis, characterized by heterogeneous clinical manifestations and variable disease progression. Ultrasonography has emerged as a valuable tool in the diagnosis and monitoring of PsA, providing real-time visualization of joint and soft tissue abnormalities. This review highlights recent advancements in ultrasonographic techniques for the assessment of PsA, including the identification of typical features, the role of power Doppler imaging in detecting active inflammation, and the potential of ultrasound for guiding treatment decisions. Additionally, we discuss the utility of ultrasound in assessing treatment response and monitoring disease progression in patients with PsA, with a focus on novel imaging modalities. By elucidating the evolving role of ultrasonography in PsA management, this article aims to enhance clinicians' understanding of its utility in facilitating early diagnosis, optimizing treatment strategies, and improving patient outcomes.

Pharmacological Management and Potentially Inappropriate Prescriptions for Patients with Acne.

Objective: Acne is a chronic inflammatory disease that involves the pilosebaceous follicle. Its pharmacological treatment involves topical and systemic medications, but a heterogeneous group of drugs may exacerbate or induce skin lesions. The aim of this study was to identify the pharmacological management and medications related to the exacerbation of skin lesions in patients diagnosed with acne. Methods: This was a cross-sectional study that identified the outpatient medication prescription patterns of patients with acne from a dispensing database of 8.5 million members of the Colombian Health System. Sociodemographic and pharmacological variables and the identification of prescriptions that were potentially inappropriate due to the risk of worsening acne were considered. Results: A total of 21,604 patients with acne were identified. Median age was 20.8 years (interquartile range: 17.3-27.3 years), and 60.7 percent were female. Treatment mainly involved antibiotics (79.9% of patients), especially doxycycline (66.0%), and retinoids (55.7%). A total of 17.2 percent of patients had potentially inappropriate prescriptions, predominantly progestogens with androgenic properties (8.9%). Female patients (odds ratio [OR]: 3.55; 95% confidence interval [CI]:3.24-3.90) and patients with pathologies such as systemic lupus erythematosus (OR: 18.61; 95% CI: 7.23-47.93) and rheumatoid arthritis (OR: 10.80; 95% CI: 5.02-23.23) were more likely to receive inappropriate prescriptions, and the risk increased with each year of life (OR: 1.02; 95% CI: 1.02-1.03). Limitations: Access to medical records was not obtained to verify clinical characteristics of acne. Conclusion: Patients with acne are excessively treated with systemic antibiotics, counter to clinical practice guidelines. Approximately one-fifth of these patients received some potentially inappropriate medication that could exacerbate their skin lesions.

Exploring in vitro modeling in hepatocarcinogenesis research: morphological and molecular features and similarities to the corresponding human disease.

The hepatocellular carcinoma (HCC) features a remarkable epidemiological burden, ranking as the third most lethal cancer worldwide. As the HCC-related molecular and cellular complexity unfolds as the disease progresses, the use of a myriad of in vitro models available is mandatory in translational preclinical research setups. In this review paper, we will compile cutting-edge information on the in vitro bioassays for HCC research, (A) emphasizing their morphological and molecular parallels with human HCC; (B) delineating the advantages and limitations of their application; and (C) offering perspectives on their prospective applications. While bidimensional (2D) (co) culture setups provide a rapid low-cost strategy for metabolism and drug screening investigations, tridimensional (3D) (co) culture bioassays - including patient-derived protocols as organoids and precision cut slices - surpass some of the 2D strategies limitations, mimicking the complex microarchitecture and cellular and non-cellular microenvironment observed in human HCC. 3D models have become invaluable tools to unveil HCC pathophysiology and targeted therapy. In both setups, the recapitulation of HCC in different etiologies/backgrounds (i.e., viral, fibrosis, and fatty liver) may be considered as a fundamental guide for obtaining translational findings. Therefore, a "multimodel" approach - encompassing the advantages of different in vitro bioassays - is encouraged to circumvent "model-biased" outcomes in preclinical HCC research.

The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Correlation and comparison between different measurement sites of waist circumference and cardiovascular risk in children: a systematic review and meta-analysis.

BACKGROUND: waist circumference (WC) is a component of metabolic syndrome (MetS) and an excellent marker for the risk of cardiovascular disease (CVD) in children. This study aimed to provide information on the anatomical measurement sites of WC and their comparative correlation with MetS and its components in children. METHODS: the literature search included papers published between January 2005 and September 2023 that met the following criteria: pediatric patients (2-18 years), WC measurement at different anatomical sites (≥ 2), and CVD risk by MetS. The quality of each study was determined using the STROBE and modified GRADE scales. The meta-analysis evaluated the WCiliac-crest and WCmiddle. RESULTS: five observational studies (total population: 1,224) were included. WC was measured at 2-4 anatomical sites. In all studies, the correlations between different WC measurement sites and CVD risk were similar. The STROBE assessment ranged from 12-20/22 and the GRADE was A for all the articles. The meta-analysis showed that the heterogeneity (I2 test) of the WCiliac-crest and WCmiddle with CVD variables was substantial. CONCLUSION: All WC measurement sites showed adequate correlation with CVD risk, with some small individual differences. WCnarrow and WCumbilucus have adequate consistency and could be excellent alternatives in daily clinical practice because of their ease of measurement. Further studies are needed to evaluate the correlation between different WC measurement sites and CVD risk in children stratified according to pubertal stage and sex.

Necropsy findings in heart transplant recipients with or without primary graft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT), but pathophysiology and histology are not completely understood. This study describes and compares morphological findings of hearts of patients with and without PGD. METHODS: We included adult patients submitted to HT in a single center who died within the first 14 days after HT and were submitted to necropsy. Clinical and histological data were recorded retrospectively. All heart slides were reviewed by a blinded pathologist. We categorized patients in two groups (PGD and non-PGD) and compared findings between them. RESULTS: Among 322 HTs, 26 patients were included. Median age was 51.5 years, 57.7% were male, 46.1% had non-ischemic cardiomyopathy, 30.8% Chagas cardiomyopathy and 23% ischemic cardiomyopathy. Eleven patients presented PGD, while 15 patients did not. PGD was severe in 72.7% of cases and moderate in 27.3%. PGD group had longer ischemic time (p=0.08), higher incidence of mechanical circulatory support (p=0.004), lower post-transplant biventricular ejection fraction (p=0.005). However, necropsy findings were similar between groups. Necrosis was detected in 80.7% of all cases (p=0.907 comparing groups), taking ≥ 10% of myocardial area in 46.1% of them, and 4 types of necrosis were found either in patients with and without PGD. CONCLUSION: Cardiac pathological findings were similar in HT patients with or without PGD who died within 14 days after the transplant and necrosis was frequent in both groups, raising the hypothesis necrosis is not the cause of cardiac dysfunction in PGD.

Comparative FEM study on intervertebral disc modeling: Holzapfel-Gasser-Ogden vs. structural rebars.

Introduction: Numerical modeling of the intervertebral disc (IVD) is challenging due to its complex and heterogeneous structure, requiring careful selection of constitutive models and material properties. A critical aspect of such modeling is the representation of annulus fibers, which significantly impact IVD biomechanics. This study presents a comparative analysis of different methods for fiber reinforcement in the annulus fibrosus of a finite element (FE) model of the human IVD. Methods: We utilized a reconstructed L4-L5 IVD geometry to compare three fiber modeling approaches: the anisotropic Holzapfel-Gasser-Ogden (HGO) model (HGO fiber model) and two sets of structural rebar elements with linear-elastic (linear rebar model) and hyperelastic (nonlinear rebar model) material definitions, respectively. Prior to calibration, we conducted a sensitivity analysis to identify the most important model parameters to be calibrated and improve the efficiency of the calibration. Calibration was performed using a genetic algorithm and in vitro range of motion (RoM) data from a published study with eight specimens tested under four loading scenarios. For validation, intradiscal pressure (IDP) measurements from the same study were used, along with additional RoM data from a separate publication involving five specimens subjected to four different loading conditions. Results: The sensitivity analysis revealed that most parameters, except for the Poisson ratio of the annulus fibers and C01 from the nucleus, significantly affected the RoM and IDP outcomes. Upon calibration, the HGO fiber model demonstrated the highest accuracy (R2 = 0.95), followed by the linear (R2 = 0.89) and nonlinear rebar models (R2 = 0.87). During the validation phase, the HGO fiber model maintained its high accuracy (RoM R2 = 0.85; IDP R2 = 0.87), while the linear and nonlinear rebar models had lower validation scores (RoM R2 = 0.71 and 0.69; IDP R2 = 0.86 and 0.8, respectively). Discussion: The results of the study demonstrate a successful calibration process that established good agreement with experimental data. Based on our findings, the HGO fiber model appears to be a more suitable option for accurate IVD FE modeling considering its higher fidelity in simulation results and computational efficiency.

Chemical characterization, in vivo safety profile and effects of the extract from unconventional food plant Acca sellowiana (O. BERG) Burret on endothelial cells under glucose overload.

"Guava" (Acca sellowiana) is an unconventional edible plant from Brazil. It is used in traditional medicine as an anti-diabetic; however, pharmacological studies on this plant are scarce. This study aimed to evaluate the chemical and safety profile of an aqueous A. sellowiana peel extract (ASPE) and its effects on endothelial EA.hy926 cells under glucose overload and in vivo (Artemia salina). An ethanolic extract from A. sellowiana peels (ASPEetOH) was also produced and characterized. Results showed that ASPE did not present in vivo toxicity, and it was found to contain high phenolic content and redox capacity. ASPE (50 µg/mL; 24 h) prevented oxidative stress and mitochondrial dysfunction, besides positively modulating Sirtuins 1 and 3, and prevented the increase of COX-2 and NF-kß expression levels in EA.hy926 cells under glucose overload. Chromatographic fractionation, metabolite profiling, spectroscopic and bioinformatics analyses revealed the presence of phenolic acids, flavan-3-ols, flavonols, flavones, flavanones, and anthocyanidins, displaying a diversity of compounds in the crude and fractionated ASPEetOH. This study provided evidence on the safety profile, chemical composition, and pharmacological activities of A. sellowiana.