Showing papers by "Federal University of São Paulo published in 2023"

Transplantation of subretinal stem cell–derived retinal pigment epithelium for stargardt disease

Abstract: To assess the safety of injecting human embryonic stem cell retinal pigment epithelial cell dose to treat Stargardt disease.In this prospective, Phase I clinical trial, human embryonic stem cell retinal pigment epithelial cells in suspension were injected into the subretinal space in eyes with the worse best-corrected visual acuity (BCVA). After vitrectomy/posterior hyaloid removal, a partial retinal detachment was created and the human embryonic stem cell retinal pigment epithelial cells were administered. Phacoemulsification with intraocular lens implantation was performed in eyes with lens opacity. All procedures were optical coherence tomography-guided. The 12-month follow-up included retinal imaging, optical coherence tomography, visual field/electrophysiologic testing, and systemic evaluation. The main outcome was the absence of ocular/systemic inflammation or rejection, tumor formation, or toxicity during follow-up.The mean baseline BCVAs in the phacoemulsification and no phacoemulsification groups were similar (1.950 ± 0.446 and 1.575 ± 0.303, respectively). One year postoperatively, treated eyes showed a nonsignificant increase in BCVA. No adverse effects occurred during follow-up. Intraoperative optical coherence tomography was important for guiding all procedures.This surgical procedure was feasible and safe without cellular migration, rejection, inflammation, or development of ocular or systemic tumors during follow-up.

Best practice for wound repair and regeneration use of cellular, acellular and matrix-like products (CAMPs)

Abstract: There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.

Mini-review: Angiotensin- converting enzyme 1 (ACE1) and the impact for diseases such as Alzheimer’s disease, sarcopenia, cancer, and COVID-19

Abstract: Ageing has been associated with comorbidities, systemic low-grade of inflammation, and immunosenescence. Hypertension is the most common morbidity and anti-hypertensives are used for more than 50%. Angiotensin-converting enzyme 1 inhibitors (ACEi) and angiotensin II receptor blockers (ARB) control blood pressure but also seem to play a role in comorbidities such as Alzheimer's disease, sarcopenia and cancer. The impact of anti-hypertensives in comorbidities is due to the expression of renin-angiotensin system (RAS) in several tissues and body fluids. Angiotensin-converting enzyme 1 (ACE1) has been linked to oxidative stress, metabolism, and inflammation. The levels and activity of ACE1 are under genetic control and polymorphisms have been correlated with susceptibility to Alzheimer's disease. In addition, some results found that ACEi and ARB users present delayed cognitive decline and reduced risk of dementia. Regarding to sarcopenia, RAS has been linked to the catabolic and anabolic pathways for muscle mass maintenance. In some studies, older adults using ACEi were highly benefited by exercise training. In cancer, RAS and its products have been shown to play a role since their inhibition in animal models modulates tumor microenvironment and improves the delivery of chemotherapy drugs. Clinically, the incidence of colorectal cancer is reduced in patients using ACEi and ARB. During the pandemic COVID-19 it was found that ACE2 receptor plays a role in the entry of SARS-CoV-2 into the host cell. ACE1 genotypes have been linked to an increased risk for COVID-19 and severe disease. In some studies COVID-19 patients taking ARB or ACEi presented better outcome.

Weight trajectories from birth to 5 years and child appetitive traits at 7 years of age: a prospective birth cohort study

Abstract: Rapid prenatal and postnatal weight gain seem to alter appetite regulation and hypothalamic functions through different pathways; however, little is known on how early life growth trajectories may influence appetitive traits in school-age. We aimed to explore the associations between weight trajectories from birth to 5 years and appetitive traits at 7. Participants were from the Generation XXI birth cohort (n 3855). Four weight trajectories were investigated: 'normal weight gain' (closely overlaps the 50th percentile in the weight-for-age curve), 'weight gain during infancy' (low birth weight and weight gain mainly during infancy), 'weight gain during childhood' (continuous weight gain since birth) and 'persistent weight gain' (always showing higher weight than the average). Appetitive traits were assessed through the Children's Eating Behaviour Questionnaire. Associations were tested using generalised linear models, adjusted for maternal and child characteristics. Compared with 'normal weight gain', those in the other growth trajectories showed greater enjoyment of food and eating in response to food stimuli (i.e. Food Responsiveness) but were less able to compensate for prior food intake and ate faster at 7 (i.e. less Satiety Responsiveness and Slowness in Eating). Also, those with 'weight gain during infancy' showed to have greater Emotional Overeating and less Emotional Undereating and were fussier. Associations were stronger if greater weight gain occurred during infancy. Early infancy seems to be a sensitive period in the development of later appetitive traits. The control of rapid growth during infancy, besides strategies focused on the overall environment where children are living, is necessary.

Modulation of angiotensin converting enzyme 2 activity in human mesangial cells treated with hydroxychloroquine

Abstract: Introduction: The occurrence of the first case caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease (COVID-19), was described in Wuhan, China, by the end of 2019, and due to its high transmissibility, the virus had a fast dissemination throughout the world. One of COVID-19 complications is acute kidney injury. The SARS-CoV-2 possesses a membrane protein which interacts with a receptor on the host cell’s surface, the angiotensin converting enzyme 2 (ACE2), important for the virus internalization into the host cell. In the beginning of the pandemic, little was known about effective drugs against it, so hydroxychloroquine (HCQ) was indicated for both treatment or prophylactic measure against COVID-19, which is currently known for not having a protective action, and may affect the kidney depending on the concentration used. The kidney which is essential in maintaining the organism’s homeostasis through the renin-angiotensin-aldosterone system (RAAS), was also one of the main target organs in the COVID-19. The basic kidney unity, the nephron, possesses mesangial cells, which are part of both the glomerulus and the mesangial matrix, and synthetize some of the RAAS components. An imbalance in the RAAS may lead to arterial hypertension, one of the comorbidities that may cause the COVID-19 aggravation. Objectives: To evaluate the RAAS components modulation in immortalized human mesangial cells (IHMC) under treatment with hydroxychloroquine (HCQ), Losartan (Los) and the association of both medicines (Los+HCQ). Methods: The IHMC were treated for 4 hours with HCQ 50 μM or 150 μM, and Los 1 μM to evaluate the effects on ACE, ACE2 and renin activities. Protein quantification and cell viability with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay were assessed by absorbance. ACE, ACE2 and renin proteolytic activities were evaluated by fluorometric assays using the substrates Z-Phe-His-Leu, APK(Dnp) and ABZ-DRVYIHPFHLVIHNQ-EDDnp, respectively. Results: Cell viability decreased after treatment with both drugs, either alone or combined. The renin activity showed no significant variation in the three groups studied. The ACE2 activity was lowered by Los, Los+HCQ, but not by HCQ alone. The expression of ACE2 detected by immunofluorescence presented no significant variation compared to the control. Conclusion: The decrease in ACE2 activity in all studied groups compared to the control, despite the protein synthesis remaining similar to the control, demonstrates that fragments of Angiotensins I and II can inhibit this activity. The ACE2 expression maintained similar levels despite treatments, which favors the SARS-CoV-2 infection process. The mechanisms involved in this process must be studied, considering that inhibiting the ACE2 activity implies in a decrease of Ang 1-7 production, compromising vasodilation. (Supported by CAPES and FAPESP This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Guided Clustering for Selecting Representatives Samples in Chemical Databases

Abstract: Machine Learning (ML) methods, from unsupervised to supervised algorithms, have been applied to solve several tasks in the Materials Science domain, such as property prediction, design of new chemical compounds, and surrogate models in molecular dynamics simulations. ML methods can also play a fundamental role in screening materials by reducing the number of compounds under scrutiny. This reduction assumes that compounds similarly represented by a given descriptor might have similar properties; thus, an unsupervised ML method, such as the K-Means algorithm, can cluster the data set and deliver a set of representative samples. However, this selection depends on the molecular representation that might not directly relate to the target property. Here, we propose a framework that lets the specialist select a set of representative samples in a guided fashion. In particular, a loop between a clustering algorithm (k-means) and an optimization method (Basin-Hopping) is implemented, which allows the system to learn feature weights to form more homogeneous clusters given the target property. The framework also offers other visual and textual functionalities to support the expert. We evaluate the proposed framework in two scenarios, and the results show that the guidance enhances clustering formations, both in coarse (few and big clusters) and fine (many small clusters) analyses.

Association of gloves change and surgical site complications in elective cesarean sections of low-risk pregnancies

Abstract: The aim of this study was to assess whether the change of gloves is associated with reduced surgical site complications of elective cesarean sections in low-risk pregnancies.A prospective and observational study was conducted, with 169 patients selected for elective cesarean sections, and divided into two groups: group 1 (N.=100) (no change of gloves); and group 2 (N.=94) (gloves changed during surgery). Fisher's Exact Test was used to test hypotheses and existence of associations between variables. The receiver operating characteristic curve (ROC) was used to determine the best value of surgical time to identify complications in the surgical site.There was significant effect on surgical time (group 1: 72.6 vs. group 2: 65.1 min, P=0.006). There was no association between changing gloves and the presence of complications of the surgical site. Approximately 22.5% of patients had at least one complication up to 60 days after cesarean section, with no association between the change of gloves and the presence of comorbidities during prenatal follow-up (P>0.999). Surgical time >70 min was able to correctly identify 59.1% of cases of surgical site complications up to 60 days after cesarean section with a false positive rate of 34% (area under ROC curve: 0.627, P=0.0126, 95% CI: 0.554-0.695).In low-risk patients submitted to elective cesarean sections, change of gloves did not reduce the incidence of complications of the surgical site. Surgical time was an independent predictor for the presence of complications of the surgical site up to 60 days after cesarean section.

Hazard Detection During Simulated Driving in Glaucoma Patients

Abstract: Précis: In this cross-sectional study, glaucoma patients showed slower reaction times (RTs) to hazardous situations when compared with control subjects during simulated driving. Worse RTs were associated with a greater magnitude of visual field loss. Purpose: The purpose of this study was to evaluate the impact of different hazardous traffic conditions on driving performance in glaucoma patients using a high-fidelity driving simulator. Methods: The cross-sectional study was performed with 52 glaucoma patients and 15 control subjects. A series of hazard scenarios were presented, such as pedestrians crossing the street unexpectedly or vehicles suddenly pulling into the driver’s lane. RTs in seconds (s) from first the evidence of a hazard to the time it took the driver to take the foot off the gas pedal (“Gas Off”) and the time it took to depress the brake pedal (“Brake On”) were compared between groups. Results: Overall, mean RTs were statistically significantly slower in glaucoma patients (3.39±3.88 s) compared with controls (2.39±1.99 s; P=0.005) for the “Brake On” task but not for the “Gas Off” task (2.74±3.42 vs. 2.13±1.91 s, respectively; P=0.120). For subjects with glaucoma, multivariable models adjusted for age, gender, race, and visual acuity demonstrated significantly slower RTs for worse values of binocular mean sensitivity for both “Gas Off” and “Brake On” tasks (1.12 and 1.14 s slower per 10 dB worse; P=0.009 and P<0.001, respectively). Subjects with glaucoma took significantly longer times to brake for smaller (low saliency) hazards compared with larger (high saliency) hazards (P=0.027). Conclusions: RTs in response to hazardous driving situations were slower for glaucoma patients compared with controls. Individualized assessment of driving fitness using hazardous scenarios in driving simulators could be helpful in providing an assessment of driving risk in glaucoma patients.

Antistatic Packaging for Electronic Devices of PTT-Based Polymer Blends, Composites, and Nanocomposites

Abstract: Due to the economic growth and the consumption of goods and services, the packaging sector presents a very favorable scenario. In the electronic components’ industry, packages must dissipate electrostatic discharges during the transport and storage of these components to ensure functionality. This special type of packaging is called antistatic packaging and is a very important sector since the electrostatic discharge of electronic products can damage and/or disable electronic devices. However, for this application, the material must have low electrical resistivity, which makes it necessary to add antistatic agents to achieve these properties. In this chapter, we will discuss the use of poly(trimethylene terephthalate) (PTT)-based polymeric blends, composites, and nanocomposites as antistatic packaging for electronic devices. As antistatic agents, carbon materials were chosen, and the use of three different antistatic agents such as carbon nanotubes (CNT), graphite, and graphene nanoplatelets is reported. Furthermore, the modification of filler in PTT-based nanocomposites, such as multiwall carbon nanotubes’ chemical functionalization (f-MWCNT); the use of the compatibilizer agent maleic anhydride-grafted PTT (PTT-g-MA); and the addition of a second phase are described and discussed in relation to the influence of these aspects on the electrical properties of PTT. As a result, PTT can be a polymeric matrix with great potential for use as an antistatic packaging, and it can be modified with CNT, graphite, or graphene nanoplatelets to achieve the electrical properties necessary for this application.

Efficacy and Safety of 5-Fluorouracil Tattooing to Repigment Idiopathic Guttate Hypomelanosis: A Split-Body Randomized Trial

Abstract: Idiopathic guttate hypomelanosis (IGH) is a common skin disorder with no standard treatment.Assess the efficacy and safety of 5-fluorouracil (5FU) compared with saline, delivered using a tattoo machine, to repigment IGH lesions.This split-body randomized single-blinded trial recruited adults with symmetrical IGH lesions. A tattoo machine was used to deliver 5FU in IGH lesions of 1 limb and saline in the contralateral limb. Outcomes were the number of achromic lesions 30 days after treatment compared with baseline, patient satisfaction, and local or systemic adverse events.Twenty-nine patients (28 women) were included. The median number of achromic lesions decreased significantly in 5FU-treated limbs (baseline: 32, interquartile range (IQR) 23-37 × post-treatment: 12, IQR 6-18, p = .000003) and saline-treated limbs (baseline: 31, IQR 24-43 × post-treatment: 21, IQR 16-31, p = .000006), but reduction was significantly more pronounced in 5FU-treated limbs ( p = .00003). All participants were satisfied or very satisfied with results on 5FU-treated limbs. There were no adverse events.5-fluorouracil delivery using a tattoo machine was more effective than saline to repigment IGH lesions, with high patient satisfaction and no adverse events.Clinicaltrials.gov : NCT02904564.