Plasma Gel Matrix as a Promising Carrier of Epigallocatechin Gallate for Regenerative Medicine.

Plasma gel (PG) is a protein matrix prepared from platelet-poor plasma and can be utilized as a drug carrier for controlled release. We previously demonstrated its applicability as a carrier of polyphosphate. Epigallocatechin-3-gallate (EGCG) is the main flavonoid found in green tea and functions as a strong antioxidant. To explore the applicability of PG as an EGCG carrier, we examined the release of EGCG from the PG matrix using an in vitro system. Pooled platelet-poor plasma (PPP) was prepared from four healthy adult male donors, mixed with EGCG, and heated at 75 °C for 10 or 20 min to prepare the PG matrix. The PG-EGCG matrix was incubated in PBS at 37 °C, and the EGCG released into PBS was determined using spectrophotometry. The antioxidant capacity was determined based on the principle of the iodine decolorization reaction. EGCG precipitated and incorporated into the PG matrix during thermal preparation. Trypsin, used to simulate the in vivo degradation of PG, released EGCG from the PG matrix over time. The released EGCG maintained its antioxidant capacity during incubation. These results indicate that thermally prepared PG matrices can be utilized as a promising EGCG carrier in the fields of tissue engineering and regenerative medicine.

Antimicrobial Activity of Methylene Blue Associated with Photodynamic Therapy: In Vitro Study in Multi-Species Oral Biofilm.

The control of infectious diseases caused by biofilms is a continuing challenge for researchers due to the complexity of their microbial structures and therapeutic implications. Photodynamic therapy as an adjunctive anti-infective treatment has been described as a possible valid approach but has not been tested in polymicrobial biofilm models. This study evaluated the effect of photodynamic therapy in vitro with methylene blue (MB) 0.01% and red LEDs (λ = 660 nm, power density ≈ 330 mW/cm2, 2 mm distance from culture) on the metabolic activity and composition of a multispecies subgingival biofilm. Test Groups LED and MB + LED showed a more significant reduction in metabolic activity than the non-LED application group (~50 and 55%, respectively). Groups LED and MB equally affected (more than 80%) the total bacterial count in biofilms. No differences were noted in the bacterial biofilm composition between the groups. In vitro LED alone or the MB + LED combination reduced the metabolic activity of bacteria in polymicrobial biofilms and the total subgingival biofilm count.

CaMKIIα mediates spermidine-induced memory enhancement in rats: A potential involvement of PKA/CREB pathway.

Memory consolidation is associated with the regulation of protein kinases, which impact synaptic functions and promote synaptogenesis. The administration of spermidine (SPD) has been shown to modulate major protein kinases associated with memory improvement, including the Ca2+-dependent protein kinase (PKC) and cAMP-dependent protein kinase (PKA), key players in the cAMP response element-binding protein (CREB) activation. Nevertheless, the initial mechanism underlying SPD-mediated memory consolidation remains unknown, as we hypothesize a potential involvement of the memory consolidation precursor, Ca2+/calmodulin-dependent protein kinase II-α (CaMKIIα), in this process. Based on this, our study aimed to investigate potential interactions among PKC, PKA, and CREB activation, mediated by CaMKIIα activation, in order to elucidate the SPD memory consolidation pathway. Our findings suggest that the post-training administration of the CaMKII inhibitor, KN-62 (0.25 nmol, intrahippocampal), prevented the memory enhancement induced by SPD (0.2 nmol, intrahippocampal) in the inhibitory avoidance task. Through western immunoblotting, we observed that phosphorylation of CaMKIIα in the hippocampus was facilitated 15 min after intrahippocampal SPD administration, resulting in the activation of PKA and CREB, 180 min after infusion, suggesting a possible sequential mechanism, since SPD with KN-62 infusion leads to a downregulation in CaMKIIα/PKA/CREB pathway. However, KN-62 does not alter the memory-facilitating effect of SPD on PKC, possibly demonstrating a parallel cascade in memory acquisition via PKA, without modulating CAMKIIα. These results suggest that memory enhancement induced by SPD administration involves crosstalk between CaMKIIα and PKA/CREB, with no PKC interaction.

Pediatric COVID-19 in Argentina: a comprehensive analysis of disease and economic burden through official data and a systematic literature review.

Background: Limited data are available on the clinical impact and economic burden of COVID-19 in the pediatric population in Argentina. We aimed to estimate the disease and economic burden of COVID-19 on children and adolescents. Methods: We analyzed official national databases and conducted a supplemental systematic review of the published literature with meta-analysis in children aged 0-18. The period of interest was from March 2020 to August 2021, before the introduction of vaccination in this age group as a national strategic plan. In addition, we used a cost of illness analysis to estimate the direct medical costs associated with COVID-19. All costs are reported in US dollars 2023. Results: A total of 450,503 confirmed COVID-19 cases and 180 multisystem inflammatory syndrome (MIS-C) were reported in Argentina in the study period. Fourteen observational clinical studies were identified. The meta-analyses of severity level from hospital patients showed that according to different studies 15%-28% of cases were asymptomatic, 68%-88% were mild or moderate, and 3%-10% were severe or critical. About 28% of children had an underlying disease. In addition, the estimated economic burden associated with COVID-19 was 80 million dollars and 4 million dollars corresponded to MISC. Conclusion: Significant impact of COVID-19 on the healthcare system and substantial economic implications for the pediatric population in Argentina were identified. The findings should help policymakers to make informed decisions and allocate resources effectively.

Dental autotransplantation: a viable solution for preserving oral health and function.

DESIGN: An umbrella review of systematic reviews and meta-analyses on dental autotransplantation (DAT). AIM: To provide a comprehensive overview of the current state of knowledge on prognostic factors, outcomes, and complications of DAT by synthesizing the evidence. METHODS: A comprehensive search of six databases was conducted for systematic reviews and meta-analyses published up to June 30, 2022. Two authors independently performed study selection, data extraction, and quality assessment using the AMSTAR 2 tool. Raw data from primary studies were analyzed using a random effects meta-analysis, and meta-regression was performed to investigate the effect of open and closed apices on the outcomes. RESULTS: Ten systematic reviews, of which nine included meta-analyses, were examined. The overall success rate of the studies was 89.4%, and the survival rate was 96.1%. The main complications were ankylosis (4.6%) and root resorption (7.4%). The analysis showed that a closed apex increased the proportion of ankylosis, resorption, and reduced survival but had no effect on success. The quality of the systematic reviews included varied, with 20% scoring moderate, 60% scoring low, and 20% scoring critically low on the AMSTAR 2 scale. CONCLUSIONS: Dental implant therapy is a reliable solution for replacing lost or damaged teeth, with high success and survival rates. However, it is a procedure that requires precision and attention to detail, along with careful selection of suitable candidates, comprehensive planning, and consideration of factors that may impact outcomes. To improve results and reduce potential complications, it is essential to establish standard clinical guidelines and conduct further extensive research.

Does Liquid/Injectable Platelet-Rich Fibrin Help in the Arthrocentesis Treatment of Temporomandibular Joint Disorder Compared to Other Infusion Options? A Systematic Review of Randomized Clinical Trials.

Temporomandibular joint disorders (TMDs) are prevalent musculoskeletal conditions involving pain and dysfunction of jaw mobility and function, which have proven difficult to treat satisfactorily. The present study aimed to assess the effectiveness of a liquid platelet-rich fibrin (i-PRF) infusion during arthrocentesis versus other options using coadjuvant materials to reduce TMD symptoms. A literature search was conducted using PubMed, EMBASE, Web of Science, Scopus, and ClinicalTrials.gov for RCTs published before January 2024, comparing i-PRF to any other TMD treatment. This systematic review was registered on PROSPERO (CRD42023495364). The searches generated several recent RCTs that compared i-PRF injection combined with arthrocentesis (AC) to AC-only or AC with platelet-rich plasma (PRP). The outcomes analyzed included measures of pain (visual analog scale, VAS), maximum mouth opening, joint sounds, and MRI-verified changes in joint structure. Across the RCTs, the addition of i-PRF injection to AC resulted in significant improvements in pain relief, joint function, mouth opening, and structural changes compared to AC-only or with PRP over follow-up periods ranging from 6 to 12 months. Current clinical evidence favors using i-PRF as an adjunct to AC rather than AC-only or AC with PRP for the treatment of TMDs. The improvements in subjective and objective outcome measures are clinically meaningful. Still, additional high-quality RCTs with larger sample sizes and longer follow-ups are required to strengthen the evidence base and better define the role of i-PRF in TMD management guidelines.

Comparative global analysis of stroke rehabilitation recommendations across income levels.

OBJECTIVE: Successful implementation of stroke rehabilitation guidelines demands high-quality practice standards tailored to targeted sociodemographic contexts. The primary objective is to determine the quality differences in post-stroke rehabilitation practice guidelines (PGs), when comparing high-income countries (HIC) and low or middle-income countries (LMIC). STUDY DESIGN AND SETTING: We conducted a scoping review of PGs in English or Spanish, published between 2012 and 2021, and providing recommendations on post-stroke rehabilitation. We used Search engines, databases, guideline libraries, gray literature, and references from previous reviews on post-stroke rehabilitation as sources of evidence. Quality assessment of PGs was performed using 6P's, ELSE, IOM, and AGREE II instruments. We evaluated each item using a scale between 0 to 3, based on the confidence of adherence to the standard. For AGREE II, we followed the instruction manual for scoring. At least two reviewers were independently involved in every step of the process. A cloud-based spreadsheet was used to chart data. We compared the results of PGs originating from HIC with those from LMIC. RESULTS: The inclusion criteria were met by 35 documents, which were subjected to evaluation. The study included 21 documents from HIC and 14 from middle-income countries (MIC). No manuscripts from low-income countries were available for inclusion in the study. The quality of PGs from MIC was found to be lower, in terms of methodological rigor and adherence to international recommendations for guidelines development. PGs from both groups of countries failed to include all target audiences and stakeholders (according to the 6P's criteria) and integration of ethical, legal, social, and economic considerations. CONCLUSION: There are gaps in the quality and availability of stroke rehabilitation guidelines worldwide, especially in LMIC. Designing and providing financial support for the implementation of high-quality guidelines will contribute to more effective implementation strategies in stroke rehabilitation programs and lead to improved patient outcomes.

Efficacy of Dynamic Magnetic Resonance Imaging in the Diagnosis of Degenerative Cervical Myelopathy: Systematic Review Protocol.

Cervical degenerative myelopathy (CDM) is a cervical spine condition resulting in clinical manifestations of spinal cord compression related to the chronic, non-traumatic, and progressive narrowing of the cervical spinal canal. Conventional magnetic resonance imaging (MRI) is the gold standard test to diagnose and assess the severity of CDM. However, the patient is in a neutral and static position during the MRI scan, which may devalue the dynamic factors of CDM, underestimating the risk of spinal cord injury related to cervical spine flexion and extension movements. Dynamic MRI is a promising technique to change this scenario. Therefore, the present review aims to answer the following question: "Is dynamic MRI of the cervical spine more accurate in diagnosing CDM than conventional MRI?". We will search for studies in the MEDLINE (via PubMed), Embase, Scopus, Web of Science, LILACS, and SciELO databases. The search strategy will contain a combination of terms related to cervical myelopathy and magnetic resonance imaging . Two independent reviewers will select studies, extract data, and assess the risk of bias. The synthesis of results will be descriptive, considering the main findings of the studies about the outcomes of interest.

Translation and Cross-cultural Adaptation of the SOSG-OQ 2.0 Questionnaire into Brazilian Portuguese.

Objective: To perform the cross-cultural adaptation and translation into Brazilian Portuguese of the Spine Oncology Study Group - Outcomes Questionnaire 2.0 (SOSG-OQ 2.0) to enable its application to Brazilian patients and to allow Brazilian researchers to use a questionnaire that is on trend in the scientific literature. Materials and Methods: The present is a basic, non-randomized, non-comparative study. The translation followed the proposal by Reichenheime and Moraes, mainly for the semantic equivalence and measurement equivalence sessions, as well as the recommendations by Coster and Mancini mainly in the translation stage. The stages were as follows: first - translation into Brazilian Portuguese; second - back-translation; third - semantic comparison; fourth - validation of the final construct. Results: The translations of the SOSG-OQ 2.0 made by three translators presented a high degree of similarity for most questions. The translators kept all question titles and subtitles, as well as their internal and external orders. Two sworn translators, with native proficiency in English, performed the back-translation of the amalgamated text. Both back-translations were quite similar, and any differences were solved through consensus between the main author and the sworn translators, and the translated text was considered the final version. Conclusion: The present study shows a translated version of the SOSG-OQ 2.0 with semantic validity with the original version published in English. As such, researchers can apply the questionnaire to the Brazilian population, adding another tool for spine surgeons to improve the monitoring of this complex group of patients.

Percutaneous Pedicle Screw for Thoracolumbar Fractures: A Long-term Follow-up.

Objective: This is a retrospective cohort study to analyze the long-term outcomes of thoracolumbar spine fracture patients who underwent minimally invasive percutaneous fixation. Methods: The cases of 17 patients with thoracolumbar spine fractures who had percutaneous fixation between 2009 and 2011 were the subject of a retrospective analysis. Clinical and radiographic variables were collected. For the clinical evaluation the questionnaires SF-36 and Oswestry were used. Radiographic parameters were evaluated using fracture's classification based on Magerls's criteria, the fractured vertebra's wedging angle, and the affected segment's segmental Cobb angle. The measures were made at different stages: before surgery, immediately after surgery, one year later, and at a late follow-up (5 years later). Trauma associated injuries, post-surgical and implant related complications were among the additional information taken into account. Results: The SF-36 questionnaire showed averages above 63,5% in all domains in the late postoperative data (from 5 years after the surgery). Oswestry questionnaire answers showed minimal or no physical limitations in 80% of the patients with a mean score of 10,8%±10,5. The average preoperative Cobb angle value was 5,53° ± 13,80° of kyphosis, the immediate postoperative 2,18° ± 13,38° of kyphosis, one year postoperative 5,26 ± 13,95° of kyphosis, and the late follow-up 8,78° ± 15,06° of kyphosis. The mean correction was 3,35°, and mean loss of correction was 6,6°. There were no complications observed, no case of neurological deficit, infection or implant failure occurred. Conclusion: Thoracolumbar vertebrae fractures can be surgically treated with positive late clinical and radiological outcomes and low complication rates using a minimally invasive percutaneous method.

Reliability, validity and acceptability of an online clinical reasoning simulator for medical students: An international pilot.

INTRODUCTION: Clinical reasoning skills are essential for decision-making. Current assessment methods are limited when testing clinical reasoning and management of uncertainty. This study evaluates the reliability, validity and acceptability of Practicum Script, an online simulation-based programme, for developing medical students' clinical reasoning skills using real-life cases. METHODS: In 2020, we conducted an international, multicentre pilot study using 20 clinical cases with 2457 final-year medical students from 21 schools worldwide. Psychometric analysis was performed (n = 1502 students completing at least 80% of cases). Classical estimates of reliability for three test domains (hypothesis generation, hypothesis argumentation and knowledge application) were calculated using Cronbach's alpha and McDonald's omega coefficients. Validity evidence was obtained by confirmatory factor analysis (CFA) and measurement alignment (MA). Items from the knowledge application domain were analysed using cognitive diagnostic modelling (CDM). Acceptability was evaluated by an anonymous student survey. RESULTS: Reliability estimates were high with narrow confidence intervals. CFA revealed acceptable goodness-of-fit indices for the proposed three-factor model. CDM analysis demonstrated good absolute test fit and high classification accuracy estimates. Student survey responses showed high levels of acceptability. CONCLUSION: Our findings suggest that Practicum Script is a useful resource for strengthening students' clinical reasoning skills and ability to manage uncertainty.

Relationship of Maxillary Sinus Volume and Nasal Septum Deviation: A Cone Beam Computed Tomography Study.

The present study was designed to test the hypothesis that there would be a correlation between nasal septum deviation (NSD) and a decreased maxillary sinus volume (MSV) in a Colombian population, using Cone Beam Computed Tomography (CBCT); other sinusal anatomical structures found during the reading were described and analyzed. A retrospective analysis of 537 CBCT scans of adult patients taken between January 2014 and January 2017 included measuring the maxillary sinus diameter in the vertical, horizontal, and sagittal planes. NSD was quantified and related to MSV using the same field of view (FOV). The volume of the right and left maxillary sinuses showed a median and interquartile range (IQR) of 8.18 mm3 (IQR: 6.2-10.33) and 8.3 mm3 (IQR: 6.4-10.36). Statistically significant differences were observed between sex and right and left MSV (p = 0.000), with higher MSV in men. The presence of NSD was observed in 96.81% of the sample and was evaluated in degrees, observing a median of 11° (IQR: 7-16) where 40% of the sample had moderate angles (9-15°). There was no correlation between NSD and a decreased MSV in the population studied. Detailed CBCT analysis with a large FOV is crucial for the analysis of anatomical structures before performing surgical procedures that involve the MS as a preventive diagnostic and therapeutic step for appropriate treatment.

Evaluation of marginal and internal adaptation of veneers generated by the guided prosthetic tooth preparation system.

OBJECTIVE: This in vitro study aimed to assess and contrast the marginal and internal adaptation of all-ceramic prefabricated veneers manufactured via the FirstFit guided tooth preparation system against all-ceramic veneers produced using the chairside Computer-Aided Design/Computer Aided Manufacture (CAD/CAM) system following identical guided preparation protocols. MATERIALS AND METHODS: Two main groups were included, with 16 lithium disilicate veneers per group. Four typodonts were used for the test (FirstFit) and control CAD/CAM groups. Intraoral scans created master casts and preparation guides. Guides performed preparations on typodont teeth (two central incisors and two lateral incisors). Prepared teeth were scanned (CEREC Omnicam) to design and mill CAD/CAM veneers. Marginal gap thickness and cement space thickness were measured using light microscopy at four locations: marginal, cervical internal, middle internal, and incisal internal. RESULTS: No significant difference existed between groups for marginal adaptation (p = 0.058) or incisal internal adaptation (p = 0.076). The control group had significantly lower values for middle internal adaptation (p = 0.023) and cervical internal adaptation (p = 0.019). CONCLUSIONS: Guided preparation evaluation showed no significant differences in marginal or incisal internal adaptation. The CAD/CAM group had significantly lower middle and cervical internal adaptation values.

Effectiveness of Oroantral Communication Closure Using Solid Platelet-Rich Fibrin Compared to a Conventional Treatment Approach: A Randomized Clinical Trial.

This study aimed to compare the effectiveness of platelet-rich fibrin clot (PRF) and conventional oroantral communication (OAC) repair techniques following tooth extractions from the maxilla. The study involved 22 patients, divided into 2 groups: a study group treated with PRF and a control group undergoing conventional OAC repair. The primary outcome measured was the effectiveness of OAC closure, with pain intensity and postoperative complications as secondary outcomes. Cone-beam computed tomography (CBCT) was used to evaluate post-extraction bone regeneration. Pain was assessed using the Visual Analogue Scale (VAS) on days 0, 1, 7, and 14 postoperatively. The results showed that the PRF group experienced a significant decrease in pain within the first 24 hours and after 7 days (P < .0001; P < .05). In contrast, complications were reported in 45.45% of patients in the conventional repair group and 18.18% in the A-PRF group. Three months postsurgery, CBCT revealed appreciable bone healing in both groups, with no significant difference (P > .05). In conclusion, the study suggests that A-PRF treatment for OACs resulted in fewer complications and quicker pain reduction than traditional repair methods, making it a promising alternative for managing OACs. However, future studies are needed to confirm these findings and establish the full therapeutic potential of PRF.

What are the emerging trends in dental composite materials in permanent teeth with occlusal cavities: self-adhesive vs traditional?

DESIGN: The research is a systematic review and meta-analysis of randomized controlled trials (RCTs). AIM: The study aimed to compare the clinical outcomes of self-adhesive flowable composite resins (SAFCs) versus conventional flowable composite resins (FCs) used in occlusal cavity restorations in permanent teeth. METHODS: This research included a search for RCTs. Multiple databases were systematically searched for RCTs with a minimum 1-year follow-up comparing SAFCs to FCs. Outcomes evaluated were retention, secondary caries, marginal adaptation, marginal discoloration, and postoperative sensitivity based on modified USPHS criteria. Risk of bias was assessed using Cochrane RoB 2 tool. Random effects meta-analyses were conducted where applicable. Certainty of evidence was rated using GRADE approach. RESULTS: Five RCTs (four parallel and one split mouth) comprising 138 patients were included. During 1- and 2-year recalls, there were generally no significant differences in clinical performance between SAFCs and FCs. However, FCs applied using the etch-and-rinse technique demonstrated statistically better marginal adaptation at 2 years (3 studies, RR 3.21, 95% CI 1.50-6.83) and marginal discoloration (4 studies, RR 3.40, 95% CI 1.10-10.48). The overall quality of evidence ranged from low to moderate. CONCLUSIONS: SAFCs showed comparable short-term outcomes to FCs in treating occlusal cavities. Further high-quality RCTs with longer follow-up are warranted to confirm long-term performance of SAFCs. Use of separate enamel etching may improve marginal adaptation and discoloration with FCs.

RE: Technical considerations in obtaining platelet-rich fibrin for clinical and periodontal research.

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The Association of Nanostructured Carbonated Hydroxyapatite with Denatured Albumin and Platelet-Rich Fibrin: Impacts on Growth Factors Release and Osteoblast Behavior.

Platelet-rich Fibrin (PRF), a second-generation blood concentrate, offers a versatile structure for bone regeneration due to its composition of fibrin, growth factors, and cytokines, with adaptations like denatured albumin-enriched with liquid PRF (Alb-PRF), showing potential for enhanced stability and growth factor dynamics. Researchers have also explored the combination of PRF with other biomaterials, aiming to create a three-dimensional framework for enhanced cell recruitment, proliferation, and differentiation in bone repair studies. This study aimed to evaluate a combination of Alb-PRF with nanostructured carbonated hydroxyapatite microspheres (Alb-ncHA-PRF), and how this association affects the release capacity of growth factors and immunomodulatory molecules, and its impact on the behavior of MG63 human osteoblast-like cells. Alb-PRF membranes were prepared and associated with nanocarboapatite (ncHA) microspheres during polymerization. MG63 cells were exposed to eluates of both membranes to assess cell viability, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The ultrastructural analysis has shown that the spheres were shattered, and fragments were incorporated into both the fibrin mesh and the albumin gel of Alb-PRF. Alb-ncHA-PRF presented a reduced release of growth factors and cytokines when compared to Alb-PRF (p < 0.05). Alb-ncHA-PRF was able to stimulate osteoblast proliferation and ALP activity at lower levels than those observed by Alb-PRF and was unable to positively affect in vitro mineralization by MG63 cells. These findings indicate that the addition of ncHA spheres reduces the biological activity of Alb-PRF, impairing its initial effects on osteoblast behavior.

Clinical, Functional, and Nutritional Efficacy of a Glutamine-Enriched Oligomeric Diet in Patients with Rectal Cancer.

AIMS: This work aims to evaluate the efficacy of nutritional supplementation with a glutamine-enriched oligomeric diet (GEOD) compared to a standard polymeric diet (SPD) in terms of oncology treatment-related diarrhea (OTRD) (frequency and consistency of stools), gastrointestinal toxicity, and functional and nutritional progress. METHODS: This prospective cohort study compared two groups of patients with rectal cancer in treatment with neoadjuvant chemotherapy and radiotherapy who were at risk of malnutrition. Patients were randomized to receive either 400 ml of GEOD or of SPD from the start of radiotherapy to 30 days after its completion. RESULTS: Eighty patients were recruited, 40 per arm. The GEOD arm had improved stool consistency and a greater reduction in the number of stools compared to the SPD arm (p < 0.001). The relative risk (RR) of developing diarrhea in the GEOD arm was 0.059 (95% CI 0.015-0.229). There was a reduced risk of developing intestinal mucositis in the GEOD arm compared to the SPD arm [RR 0.202 (95% CI 0.102 - 0.399)]. The GEOD arm had greater improvements in functional and nutritional status (p < 0.001). CONCLUSIONS: GEOD had a protective effect in terms of the development of gastrointestinal toxicity associated with chemotherapy and radiotherapy treatment in patients with rectal cancer.

Echinodorus macrophyllus: Acute toxicological evaluation of hydroxycinnamoyl derivatives from SF1 subfractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinodorus macrophyllus (Kunth.) Micheli (Alismataceae), known as chapéu-de-couro in Brazil, is popularly used to treat inflammatory diseases. We have previously demonstrated a significant reduction in the acute inflammation for the aqueous extract of E. macrophyllus (AEEm) and its ethanolic fraction (Fr20) and described that hydroxycinnamoyl derivatives present in SF1 (Fr20 subfraction) showed higher anti-inflammatory properties by mechanisms that include a reduction of TNF-α, IL-1ß, CKCL1/KC, LTB4, and PGE2 levels in exudate. AIM OF THE STUDY: This work describes the acute toxicological effect of SF1 subfraction on SW mice treated orally for five days in the air pouch model by evaluating the hematological and biochemical determinations on the blood samples; the relative organ weight and its histopathological analysis; the liver genotoxicity assessment and the activity of liver enzymes from xenobiotic metabolism. MATERIALS AND METHODS: Fr20 was earlier fractionated on the Sephadex LH-20 column, yielding mainly four subfractions, including SF1. The SF1 toxicity was evaluated in mice challenged with carrageenan on the air pouch inflammation model and orally treated for five days. The body weight was monitored daily, and the organs were weighed after the euthanasia. Hematological and biochemical determinations were carried out using specific commercial kits and following the protocols provided by the manufacturers. The organs were fixed, sectioned, processed for hematoxylin and eosin staining, and analyzed by light microscopy. Genotoxicity assessment was performed by the alkaline single-cell gel electrophoresis. Livers were processed for ethoxyresorufin-O-deethylase (EROD) and Glutathione S-transferase (GST) assays. RESULTS: SF1 exhibited low toxicity, as no significant discrepancy was observed in the relative weight of the body organs of mice. Moreover, the daily treatment with SF1 did not alter the number and percentage of red blood cells or hemoglobin concentration in the blood. The treatment with SF1 did not affect the creatinine concentration, but the 25 mg/kg dose reduced the plasma urea level and uric acid, suggesting its use in treating acute renal failure. The parameters analyzed did not present biochemical alterations indicative of liver disease. Regarding serum triglyceride and cholesterol levels, a significant decrease was detected in both parameters in mice treated with SF1. In addition, the histopathological analysis showed that inflammatory focus in the livers seemed more relevant in the control groups than in those treated. There were no significant changes in the renal or splenic tissues of animals treated with SF1. Treatment with SF1 also does not have a genotoxic effect on liver cells. CONCLUSION: Treatment with SF1 showed no toxicity in mice at doses equivalent to those recommended for humans, which provides evidence of the safety of the therapeutic use of this subfraction.

Recurrence After Biopsy-Confirmed Cervical High-Grade Intraepithelial Lesion Followed by Negative Conization: A Systematic Review and Meta-analysis.

ABSTRACT: The aim of the study is to assess the recurrence rate (as cervical intraepithelial neoplasia 2+ [CIN2+]) in patients who had a confirmed high-grade squamous intraepithelial lesion (CIN2-3) in a cervical biopsy specimen followed by a negative conization specimen. MATERIALS AND METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Ovid/MEDLINE, Ovid/Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception until January 2023. The study protocol was registered in PROSPERO (ID number CRD42023393951). The search identified 3,089 articles; 1,530 were removed as duplicates, and 1,559 titles and abstracts were assessed for inclusion. The full text of 26 studies was assessed for eligibility, and finally, 12 studies with 1,036 patients were included. All included studies were retrospective cohort studies. A proportion meta-analysis was performed. RESULTS: For patients with negative conization specimens, the recurrence rate as CIN2+ during follow-up was 6% (95% CI, 1.8%-12.1%; I2 = 49.2; p < .0001, 215 patients and 4 studies) in the proportion meta-analysis, ranging from 0.3% to 13.0% for the individual studies. For patients with ≤CIN1 conization specimens, the recurrence rate as CIN2+ during follow-up was 3.6% (95% CI, 1.2%-7%; I2 = 75.1; p < .0001, 991 patients and 10 studies) in the proportion meta-analysis and ranged from 0.6% to 13.0% for the individual studies. CONCLUSIONS: The recurrence rate as CIN2+ for patients with a confirmed high-grade intraepithelial lesion on a cervical biopsy followed by a negative conization specimen is 6%. In patients with negative and CIN1 conization specimens, the recurrence rate is 3.6%.