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The study of circulating peptides in the blood offers significant opportunities for diagnosing, stratifying, and managing various diseases. With recent technological advances and the ongoing need to understand complex diseases such as acute leukemias (AL), peptidomic analysis of peripheral blood, especially serum and plasma, has become increasingly important for studying human biology and pathophysiology. Here, we provide insights and perspectives on technological developments and potential clinical applications using widely used peptidomic analysis methods. We discuss examples where peptidomics using serum or plasma has contributed to the understanding of AL. Specifically, we highlight the scarcity of peptidomic studies applied to AL and emphasize the importance of exploring this area, as the few published studies present promising results that can significantly contribute to precision medicine.

The primary objective of this systematic review study was to investigate the effectiveness, durability, and adverse events of PLLA treatment for aesthetic indications. The search strategy was performed in MEDLINE (Ovid). The electronic literature search of five databases was performed, from the inception of the databases until the 12th of February 2024. This was to identify randomized clinical trials that assessed PLLA treatment in adult individuals exhibiting facial aging and/or facial lipoatrophy. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2). Eleven RCTs out of 1467 identified citations were included. Four studies showed increased dermal thickness, significant improvement in facial lipoatrophy severity and aesthetic clinical scores, after PLLA treatment with its effects sustained for at least 25 months. Two studies demonstrated the superiority of PLLA over injectable human collagen. Also, three studies showed positive results favoring PLLA when compared with PH gel in lipoatrophy severity, transepidermal water loss, skin quality, elasticity, and patient satisfaction. All adverse events were mild-to-moderate in intensity, and the main ones worth noting were bruising, hematoma, tenderness, nodules, and edema. Five out of eleven studies were considered having high risk of bias. The evidence on the effectiveness and safety of PLLA for facial rejuvenation is of low quality; thus, the reported high effectiveness, safety, and long-lasting effects for this purpose should be further investigated.

Brazil is one of the countries most affected by COVID-19, with the highest number of deaths recorded. Brazilian Health Institutions have reported four main peaks of positive COVID-19 cases. The last two waves were characterized by the emergence of the VOC Omicron and its sublineages. This study aimed to conduct a retrospective surveillance study illustrating the emergence, dissemination, and diversification of the VOC Omicron in 15 regional health units (RHUs) in MG, the second most populous state in Brazil, by combining epidemiological and genomic data. A total of 5643 confirmed positive COVID-19 samples were genotyped using the panels TaqMan SARS-CoV-2 Mutation and 4Plex SC2/VOC Bio-Manguinhos to define mutations classifying the BA.1, BA.2, BA.4, and BA.5 sublineages. While sublineages BA.1 and BA.2 were more prevalent during the third wave, BA.4 and BA.5 dominated the fourth wave in the state. Epidemiological and viral genome data suggest that age and vaccination with booster doses were the main factors related to clinical outcomes, reducing the number of deaths, irrespective of the Omicron sublineages. Complete genome sequencing of 253 positive samples confirmed the circulation of the BA.1, BA.2, BA.4, and BA.5 subvariants, and phylogenomic analysis demonstrated that the VOC Omicron was introduced through multiple international events, followed by transmission within the state of MG. In addition to the four subvariants, other lineages have been identified at low frequency, including BQ.1.1 and XAG. This integrative study reinforces that the evolution of Omicron sublineages was the most significant factor driving the highest peaks of positive COVID-19 cases without an increase in more severe cases, prevented by vaccination boosters.

A long-term indwelling catheter may be indicated in clinical situations, such as chronic diseases of the genitourinary or neurological systems. In addition to the risks of infection, trauma, and bleeding, a catheter's permanence can affect psycho-emotional and socioeconomic dimensions. We aimed to understand how the need to use a long-term indwelling catheter affects this patient's self-perception, interrelationships, and self-care. We carried out a qualitative, descriptive study based on interviews with 17 patients, and applied thematic analysis and complex thinking. The different prognoses and expectations regarding the catheter influenced self-perception, adaptation, acceptance, or denial. The presence of a catheter, whether as a curative measure or for comfort, can affect self-image and sexuality, and generate insecurities and uncertainties, which require understanding the multidimensionality of situations that suffer interference from the personal, family, and social environment, as well as health systems' capacity to deal with it. Despite the challenges, the majority of participants reported a favorable disposition towards self-care, whether to enable catheter removal or to prevent injuries in lifelong indications.

Background: The intensity of dengue virus (DV) replication and circulating non-structural protein 1 (NS1) levels may promote changes in the human immune response and favor severe forms of infection. We investigated the correlations between NS1 with CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels, and IFN-γ receptor α chain (CD119) expression, and CXCL10 production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IFN-γ in DV-infected patients with different clinical forms., Methods: Dengue virus NS1, CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels were measured in 152 DV-infected patients with different clinical forms and 20 non-infected individuals (NI) using enzyme-linked immunosorbent assay (ELISA). In addition, we investigated the CXCL-10 production after in vitro IFN-γ stimulation of PBMCs from 48 DV-infected individuals (with different clinical forms of dengue fever) and 20 NI individuals using ELISA, and CD119 expression on CD14+ cells with flow cytometry., Results: Patients with dengue hemorrhagic fever (DHF) had significantly higher NS1, CXCL-8, and CXCL-10 serum levels than those with classic dengue fever (DF). The response of PBMCs to IFN-γ stimulation was lower in patients with DHF than in those with DF or dengue with complications (DWC), with lower CD119 expression and reduced CXCL-10 synthesis. In addition, these alterations are associated with high NS1 serum levels., Conclusions: Patients with DHF reported high NS1 levels, low CD119 expression, and low CXCL-10 synthesis in PBMCs, which may be associated with infection progression and severity.

Objective: The objective of the research was to carry out a comparative study between Smith & Nephew ® or Zimmer ® prostheses with thick versus thin polyethylene, in patients undergoing primary total knee arthroplasty, during a short-term follow-up. Thus, the objective was to analyze the survival of the implants in question under the clinical and radiographic aspect., Methods: The sample was divided into two groups: Group 1 with thick polyethylene and group 2 with thin polyethylene. A clinical analysis of the patients was carried out and the implants were checked for loosening., Results: The groups were similar when compared. According to the Ahlbäck classification, 83% of the patients were in groups IV and V. The median functional score in the postoperative period was similar between the two groups. Postoperatively, the tibiofemoral angle fluctuated between 5 and 6 0 valgus on average. Two complications were observed in each group. None of the evaluated patients presented implant loosening., Conclusion: Patients treated with thick polyethylene had the same functional score as the control group, as well as the absence of radiographic changes in this short-term follow-up, with implant survival and a similar rate of complications between both groups. Level of evidence III, Retrospective study., Competing Interests: All authors declare no potential conflict of interest related to this article.

Salacia grandifolia is naturally found in the Atlantic Forest regions of Brazil. Despite the pharmacological potential of plants from the Salacia genus, phytochemical studies on this species have not been reported in literature. A new triterpene, 28-hydroxyfriedelane-3,15-dione ( 1 ), and seven known compounds (friedelan-3-one ( 2 ), friedelan-3β-ol ( 3 ), friedelane-3,15-dione ( 4 ), 15α-hydroxyfriedelan-3-one ( 5 ), 28-hydroxyfriedelan-3-one ( 6 ), 30-hydroxyfriedelan-3-one ( 7 ), and 29-hydroxyfriedelan-3-one ( 8 )) were obtained from the hexane extract of Salacia grandifolia leaves. These isolated compounds and three extracts, hexane ( EH ), chloroform ( EC ), and ethyl acetate ( EAE ), were assessed for their potential biological activities, which consisted in the evaluation of antiviral activity against a murine coronavirus, mouse hepatitis virus 3 (MHV-3), antibacterial activity against the susceptible and methicillin-resistant Staphylococcus aureus (MRSA), and antileukemia activity against the THP-1 and K-562 cell lines. The extracts EH and EAE along with the triterpenes 1 and 6 exhibited moderate to high antiviral activity, with emphasis on 6 , which presented an EC 50 value of 2.9 ± 0.3 μM. None of the compounds presented antibacterial activity against the tested strains. The evaluated compounds 1 , 4 , 6 and 7 exhibited low cytotoxic activity against the tested leukemia cell lines. Taken together, this study comprises an overview for the potential of the Salacia grandifolia biological activities, including a new isolated triterpene., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Physical examination of knee ligament injuries often is considered subjective and imprecise as the result of various factors affecting its reliability. Magnetic resonance imaging is widely used but lacks information on ligament function and is costly. Stress radiography is commonly employed, but alternatives are sought because of radiation exposure and the need for a physician's presence during the procedure. Ultrasonography represents a noninvasive, rapid, and cost-effective method for assessing knee injuries. This Technical Note presents stress ultrasonography protocols for evaluating medial and lateral tibiofemoral openings in patients with posteromedial corner and/or posterolateral corner injuries. The ultrasonography examination parameters are detailed for both the medial collateral ligament and lateral collateral ligament evaluation. Studies have associated certain degrees of tibiofemoral opening with knee ligament injuries, aiding surgeons in surgical decision-making. Examination with stress ultrasonography offers a dynamic and reproducible method without adverse effects for patients, potentially expediting the diagnosis and treatment of multiligament knee injuries., Competing Interests: The authors report the following potential conflicts of interest or sources of funding: J.L.R.D.F. reports personal fees from Sintegra Surgical Sciences, outside the submitted work. R.F.L. reports other from Arthrex, Ossur, Smith & Nephew, Elsevier, Linvatec, outside the submitted work. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2024 The Authors.)

SARS-CoV-2 is the virus responsible for a respiratory disease called COVID-19 that devastated global public health. Since 2020, there has been an intense effort by the scientific community to develop safe and effective prophylactic and therapeutic agents against this disease. In this context, peptides have emerged as an alternative for inhibiting the causative agent. However, designing peptides that bind efficiently is still an open challenge. Here, we show an algorithm for peptide engineering. Our strategy consists of starting with a peptide whose structure is similar to the interaction region of the human ACE2 protein with the SPIKE protein, which is important for SARS-COV-2 infection. Our methodology is based on a genetic algorithm performing systematic steps of random mutation, protein-peptide docking (using the PyRosetta library) and selecting the best-optimized peptides based on the contacts made at the peptide-protein interface. We performed three case studies to evaluate the tool parameters and compared our results with proposals presented in the literature. Additionally, we performed molecular dynamics (MD) simulations (three systems, 200 ns each) to probe whether our suggested peptides could interact with the spike protein. Our results suggest that our methodology could be a good strategy for designing peptides.

Objective : To compare the function and muscle strength of the limb between patients undergoing knee arthroplasties using primary implants with posterior stabilization (control group) and patients with rotating hinge implants (Hinge group). Methods : Function assessment was performed using the Knee Society Score (KSS) and muscle strength using an isokinetic dynamometer using a speed of 60°/s. Results : 43 patients were analyzed, who underwent 51 surgeries, with the Hinge group comprising 25 surgeries and the control group comprising 26 primary surgeries. We did not observe significant differences between the Hinge and control groups in the values of functional KSS (p = 0.54), objective KSS (p = 0.91), peak flexor torque (p = 0.25) and peak extensor torque (p = 0.08). Patients in the Hinge group who underwent primary arthroplasties had a higher peak flexor torque (0.76 Nm/kg) than those who used the implant in revision after septic failure (0.33 Nm/kg) (p < 0.05). The constrained implant was indicated in arthroplasty revision surgeries with severe ligament instability and in cases of complex primary arthroplasties with bone destruction or severe coronal deformity in the coronal plane. Conclusion : The use of constrained implants enables joint function and muscle strength comparable to patients who underwent primary arthroplasty using conventional implants with posterior stabilization. Patients undergoing septic revision with a rotating Hinge prosthesis exhibit lower flexor muscle strength compared to those undergoing primary arthroplasty with a constrained implant., Competing Interests: Conflito de Interesses Os autores declaram que não têm conflito de interesses, (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

This study described integrative community therapy (ICT) in the online modality as a health promotion resource in the context of COVID-19 in Latin America, characterizing the ICT circles, the ICT training centers, and the community therapists involved in this practice. It is a descriptive, observational, and cross-sectional study with a quantitative approach. Data were collected from November 2020 to July 2021 through an online questionnaire created on the Google Forms platform. The study's first stage involved the participation of ICT training centers, while the second involved community therapists. Forty-three centers participated in the first stage; 86.1% offered online ICT in the period evaluated, and 74.4% trained professionals to implement this modality. In the second stage, 66 community therapists responded to the questionnaire. Of these, 49 (74.2%) resided in Brazil, 84.8% were female, and 72.7% performed the work voluntarily, with an average of 6.1 hours per week dedicated to online circles. Community-based circles were the most cited, followed by those linked to the public sector, with an average of 20.7 participants/circle in the period. The most frequent themes were stress and negative emotions, problems with work/unemployment, and family conflicts. Strengthening self-care, participation in ICT circles, and personal empowerment stood out among the coping strategies. In conclusion, online ICT proved to be an innovative resource for health promotion during the pandemic through the articulation and engagement of community therapists and different institutions, expanding solidary social networks, and showing itself as a sustainable practice in the Latin American scenario., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Body Harmonization (BHA) is an innovative concept in aesthetics area based on a set of advanced injectable techniques that have shown promising results for body shaping. This is based on procedure combinations indicated to treat body aesthetic dysfunctions, such as localized fat, stretch marks, blemishes, flaccidity, buttocks remodeling, lean mass gain and muscle definition. This study aims to define the clinical concept of BHA, its applications and the main protocols used based on injectable pharmacotherapy. For this purpose, we performed a retrospective review of proven efficient injectable procedures with advanced results for the treatment of body aesthetic disorders, in addition to relying on data obtained from previous clinical experiences. Based on these data, we describe how different compounds can act for treatment of the main body aesthetic dysfunctions, such as lipolytic compounds and collagen biostimulators. In addition, the main application techniques and treatment protocols for each of these dysfunctions were defined. Minimally invasive injectable procedures offer an effective therapeutic option for patients who do not intend to undergo surgical interventions., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Barbosa et al.)

Opportunistic fungal infections represent a global health problem, mainly for immunocompromised individuals. New therapeutical options are needed since several fungal strains show resistance to clinically available antifungal agents. 2-Thiazolylhydrazones are well-known as potent compounds against Candida and Cryptococcus species. A scaffold-focused drug design using machine-learning models was established to optimize the 2-thiazolylhydrazone skeleton and obtain novel compounds with higher potency, better solubility in water, and enhanced absorption. Twenty-nine novel compounds were obtained and most showed low micromolar MIC values against different species of Candida and Cryptococcus spp., including Candida auris , an emerging multidrug-resistant yeast. Among the synthesized compounds, 2-thiazolylhydrazone 28 (MIC value ranging from 0.8 to 52.17 μM) was selected for further studies: cytotoxicity evaluation, permeability study in Caco-2 cell model, and in vivo efficacy against Cryptococcus neoformans in an invertebrate infection model. All results obtained indicate the great potential of 28 as a novel antifungal agent.

Introduction: In the present study, the impact of BromAc®, a specific combination of bromelain and acetylcysteine, on the SARS-CoV-2-specific inflammatory response was evaluated., Methods: An in vitro stimulation system was standardized using blood samples from 9 healthy donors, luminex assays and flow cytometry were performed., Results and Discussion: BromAc® demonstrated robust anti-inflammatory activity in human peripheral blood cells upon SARS-CoV-2 viral stimuli, reducing the cytokine storm, composed of chemokines, growth factors, and proinflammatory and regulatory cytokines produced after short-term in vitro culture with the inactivated virus (iSARS-CoV-2). A combined reduction in vascular endothelial growth factor (VEGF) induced by SARS-CoV-2, in addition to steady-state levels of platelet recruitment-associated growth factor-PDGFbb, was observed, indicating that BromAc® may be important to reduce thromboembolism in COVID-19. The immunophenotypic analysis of the impact of BromAc® on leukocytes upon viral stimuli showed that BromAc® was able to downmodulate the populations of CD16+ neutrophils and CD14+ monocytes observed after stimulation with iSARS-CoV-2. Conversely, BromAc® treatment increased steady-state HLA-DR expression in CD14+ monocytes and preserved this activation marker in this subset upon iSARS-CoV-2 stimuli, indicating improved monocyte activation upon BromAc® treatment. Additionally, BromAc® downmodulated the iSARS-CoV-2-induced production of TNF-a by the CD19+ B-cells. System biology approaches, utilizing comprehensive correlation matrices and networks, showed distinct patterns of connectivity in groups treated with BromAc®, suggesting loss of connections promoted by the compound and by iSARS-CoV-2 stimuli. Negative correlations amongst proinflammatory axis and other soluble and cellular factors were observed in the iSARS-CoV-2 group treated with BromAc® as compared to the untreated group, demonstrating that BromAc® disengages proinflammatory responses and their interactions with other soluble factors and the axis orchestrated by SARS-CoV-2., Conclusion: These results give new insights into the mechanisms for the robust anti-inflammatory effect of BromAc® in the steady state and SARS-CoV-2-specific immune leukocyte responses, indicating its potential as a therapeutic strategy for COVID-19., Competing Interests: SV and DM are shareholders of Mucpharm Pty Ltd. and provided scientific input on the protocol and design of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Mucpharm Pty Ltd. The funder had the following involvement in the study: provided only scientific input on the protocol and design of the study., (Copyright © 2023 Ferreira, Clarindo, Ribeiro, Gomes-de-Pontes, de Carvalho, Martins-Filho, da Fonseca, Teixeira, Sabino, Eapen, Morris, Valle and Coelho-dos-Reis.)

Objective  This study assessed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of serological tests, synovial fluid markers, microbiological tissue culture, and histopathological examination of the periprosthetic membrane in diagnosing periprosthetic knee infection. Methods  This study is prospective, and it includes patients undergoing total knee arthroplasty revision surgery from November 2019 to December 2021. The analysis consisted of serological tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and D-dimer), synovial fluid markers (leukocyte and polymorphonuclear cell counts), periprosthetic tissue culture, and histopathological examination of the periprosthetic membrane of all patients. Results  Sixty-two patients had periprosthetic joint infection (PJI) according to the 2018 International Consensus Meeting criteria (infection group), while 22 subjects had no infection. ESR sensitivity and specificity were 83.6% and 45.4%, respectively. CRP sensitivity and specificity were 64.5% and 100%, whereas D-dimer sensitivity and specificity were 78.9% and 25%, respectively. Leukocyte count sensitivity and specificity were 75.6% and 100%, polymorphonuclear cell count sensitivity and specificity were 33% and 100%, respectively. Periprosthetic tissue culture sensitivity and specificity culture were, respectively, 77.4% and 100%. Histopathological examination sensitivity and specificity were 43.7% and 100%, respectively. Conclusions  In our study, the total blood cell count in synovial fluid and microbiological cultures of periprosthetic tissues were the most accurate tests for PJI diagnosis. In contrast, polymorphonuclear cell percentage was the least accurate test for PJI diagnosis., Competing Interests: Conflito de Interesses Os autores não têm conflitos de interesse a declarar., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy., Objective: This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO)., Methods: This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%., Results: The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group., Conclusion: GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Background: Biomechanical assessment of meniscal repairs is essential for evaluating different meniscal suturing methods and techniques. The continuous meniscal suture technique is a newer method of meniscal repair that may have biomechanical differences compared with traditional techniques., Purpose: To evaluate the displacement, stiffness after cyclical loading, and load to failure for a continuous vertical inside-out meniscal suture versus a traditional vertical inside-out meniscal suture in a porcine medial meniscus., Study Design: Controlled laboratory study., Methods: A total of 28 porcine knees were acquired and divided into 2 test groups of 14 medial meniscus each. A 2.0-cm longitudinal red-white zone cut was made in the body of the medial meniscus for each knee. The continuous suture (CS) group received 4 vertical stitches performed with a continuous vertical meniscal suture technique, and the inside-out suture (IO) group received a traditional vertical suture with 4 stitches. Two traction tapes were passed between the sutures and positioned in the biomechanical testing fixture device. Each specimen underwent load-to-failure testing at 5 mm/s, and displacement, system stiffness, and maximum load to failure were compared between the groups., Results: The displacement after the cyclic test was 0.53 ± 0.12 and 0.48 ± 0.07 mm for the CS and IO groups, respectively. There was no significant difference between the groups ( P  = .2792). The stiffness at the ultimate load testing was 36.3 ± 1.9 and 35.3 ± 2.4 N/mm for groups CS and IO, respectively, with no significant difference between the groups ( P  = .2557). In the load-to-failure test, the ultimate load was 218.2 ± 63.9 and 238.3 ± 71.3 N in the CS and IO groups, respectively, with no significant group differences ( P  = .3062)., Conclusion: A continuous vertical meniscal suture created a configuration for treating longitudinal meniscal lesions that was beneficial and biomechanically similar to a traditional vertical suture technique., Clinical Relevance: The study findings indicate that use of the continuous vertical inside-out meniscal suture technique is a possible therapeutic option., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Research support and material were received from Síntegra Surgical Sciences. J.L.R.d.F. has received nonconsulting fees from Síntegra Surgical Sciences, grants from Síntegra Surgical Sciences, and has 2 patents pending. R.F.L. has received royalties from Arthrex, Ossur, Smith & Nephew, and Elsevier; consulting fees from Smith & Nephew and Ossur; and nonconsulting fees from Smith & Nephew and Linvatec. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval was not sought for the present study., (© The Author(s) 2023.)

The present work aimed to characterize and compare the catalytic properties of amylases from Cunninghamella echinulata and Rhizopus microsporus. The highest production of amylase by C. echinulata, 234.94 U g-1 of dry substrate (or 23.49 U mL-1), was obtained using wheat bran as a substrate, with 50-55% initial moisture and kept at 28 °C for 48 h. The highest production of amylases by R. microsporus, 224.85 U g-1 of dry substrate (or 22.48 U mL-1), was obtained cultivating wheat bran with 65% initial moisture at 45 °C for 24 h. The optimal activity of the amylases was observed at pH 5.0 at 60 °C for C. echinulata enzymes and at pH 4.5 at 65 °C for R. microsporus. The amylases produced by C. echinulata were stable at pH 4.0-8.0, while the R. microsporus enzymes were stable at pH 4.0-10.0. The amylases produced by C. echinulata remained stable for 1 h at 50 °C and the R. microsporus amylases maintained catalytic activity for 1 h at 55 °C. The enzymatic extracts of both fungi hydrolyzed starches from different plant sources and showed potential for liquefaction of starch, however the amylolytic complex of C. echinulata exhibited greater saccharifying potential.

We investigated three calcium silicate-based sealers with respect to their chemical characterization, cytotoxicity, and attachment to RAW264.7 cells. BioRoot RCS (BR), Bio-C Sealer (BC), and Sealer Plus BC (SPBC) were assessed using Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), and energy-dispersive X-ray spectroscopy (EDX) (n = 4) for elemental characterization, and using scanning electron microscopy (SEM) to evaluate cell morphology and adhesion. Cytotoxicity was determined at different dilutions (1:1, 1:2, and 1:5) using the succinate dehydrogenase activity (MTT assay). Statistical analysis was performed for normal distribution using the Shapiro-Wilk test and for homoscedasticity using Levene's test, and one-way ANOVA, Tukey's/Dunnett's post hoc tests for cell viability and XRF (α = 0.05). Calcium silicate hydrate and calcium hydroxide were detected by FTIR in all groups. EDX detected a higher calcium content for BR and SPBC and aluminum only in the premixed sealers. XRF detected the highest calcium release in BR ( p < 0.05). The surface morphology showed irregular precipitates for all the sealers. SPBC at a 1:2 dilution resulted in the lowest cell viability compared to BR ( p < 0.05) and BC ( p < 0.05). The calcium silicate-based sealers produced a statistically significant reduction in cellular viability at a 1:1 dilution compared to the control group ( p < 0.0001). All the sealers maintained viability above 70%.

Objective  We studied the microbiological profile of periprosthetic knee infections treated in a Brazilian tertiary hospital. Methods  The study included all patients undergoing revision surgery for total knee arthroplasty (RTKA) between November 2019 and December 2021, with a diagnosis of periprosthetic infection confirmed per the 2018 International Consensus Meeting (ICM) criteria. Results  Sixty-two patients had a periprosthetic joint infection (PJI) per the 2018 ICM criteria. Cultures were monomicrobial in 79% and polymicrobial in 21% of cases. The most frequent bacterium in microbiological tissue and synovial fluid cultures was Staphylococcus aureus , observed in 26% of PJI patients. Periprosthetic joint infection with negative cultures occurred in 23% of patients. Conclusion  Our results show the following: i) a high prevalence of Staphylococcus as an etiological agent for knee PJI; ii) a high incidence of polymicrobial infections in early infections; iii) the occurrence of PJI with negative cultures in approximately one fourth of the subjects., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Breast cancer is the most common cancer and the most frequent cause of death in women. Doxorubicin, an anthracycline, is an important drug due to its efficacy in treating solid cancers, especially breast cancer. However, this drug is often responsible for cardiotoxicity that may affect more than 25% of patients. This study aimed to evaluate the red cell distribution width (RDW) in women with breast cancer to monitor adverse events associated with the use of doxorubicin. A prospective study of 80 women with breast malignancy undergoing neoadjuvant doxorubicin-based chemotherapy was conducted. The patients were evaluated at baseline (T0), just after the last cycle of chemotherapy with doxorubicin (T1), and 1 year after the treatment (T2). There was a significant increase over the time points for the RDW ( p < 0.001). There was a negative correlation between the RDW and C-reactive protein (CRP) levels at T1. The RDW did not show a significant difference between the groups classified according to cardiotoxicity. Based on these results, the RDW is a cost-effective test that shows a relationship with the doxorubicin response, but not with cardiotoxicity. It is a potential biomarker to evaluate patients with breast cancer after they receive chemotherapy with doxorubicin.

Since its first identification in Brazil, the variant of concern (VOC) Gamma has been associated with increased infection and transmission rates, hospitalizations, and deaths. Minas Gerais (MG), the second-largest populated Brazilian state with more than 20 million inhabitants, observed a peak of cases and deaths in March-April 2021. We conducted a surveillance study in 1240 COVID-19-positive samples from 305 municipalities distributed across MG's 28 Regional Health Units (RHU) between 1 March to 27 April 2021. The most common variant was the VOC Gamma (71.2%), followed by the variant of interest (VOI) zeta (12.4%) and VOC alpha (9.6%). Although the predominance of Gamma was found in most of the RHUs, clusters of Zeta and Alpha variants were observed. One Alpha-clustered RHU has a history of high human mobility from countries with Alpha predominance. Other less frequent lineages, such as P.4, P.5, and P.7, were also identified. With our genomic characterization approach, we estimated the introduction of Gamma on 7 January 2021, at RHU Belo Horizonte. Differences in mortality between the Zeta, Gamma and Alpha variants were not observed. We reinforce the importance of vaccination programs to prevent severe cases and deaths during transmission peaks.

Myelodysplastic neoplasms are clonal hematological malignancies arising from hematopoietic stem cells that accumulate various mutations. MDS is heterogeneous in nature but uniformly characterized by ineffective hematopoiesis, dysplasia of one or more cell lineages, and an increased risk of transformation to acute myeloid leukemia. Disease-related risk is commonly assessed using the Revised International Prognostic Scoring System based on five cytogenetic risk groups, together with refined categories for bone marrow blast percentage and number of cytopenias. Therapeutic options for patients with MDS vary from supportive care to allogeneic stem cell transplantation depending on the disease and patient-related risk factors. Despite great progress in understanding the molecular mechanisms underlying MDS, this knowledge has not yet been translated into the approval of a curative treatment., Competing Interests: Conflicts of interest The authors declare that there are no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: In recent decades, the world watched a dramatic increase in the incidence of acute coronary syndromes (ACS) among young individuals (≤55 years-old) and a relative decrease in the elderly. The management of ACS in young patients with multivessel disease still needs to be elucidated, as these individuals maintain a long life expectancy., Research Question: To compare clinical outcomes and care costs in individuals with premature ACS and multivessel disease undergoing coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI)., Methods and Results: Participants included all individuals ≤55 years-old admitted with ACS to public hospitals in Brasília (Brazil) between 2013 and 2015 and who underwent cardiac catheterization with SYNTAX score ≥23 or Duke category 6. Outcomes were adjudicated with death certificates and data from medical records. The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as death due to cardiovascular causes, recurrent hospitalizations due to cardiovascular ischemic events, and incident heart failure New York Heart Association III-IV. As secondary outcome we assessed indirect and direct costs by evaluating the cost of lost productivity (in international dollars (Int$) per year) due to illness and death, outpatient costs and costs with new hospitalizations. Multivariate and principal components (PC) adjusted analyzes were performed., Results: Among 1,088 subjects (111 CABG and 977 PCI) followed for 6.2 years (IQR: 1.1), 304 primary events were observed. MACE was observed in 20.7% of the CABG group and 28.8% of the PCI group ( p = 0.037). In multivariate analyses, PCI was associated with a hazard ratio (HR) = 1.227 (95% CI: 1.004-1.499; p = 0.0457) for MACE, and in PC-adjusted HR = 1.268 (95% CI: 1.048-1.548; p = 0.0271) compared with CABG. Despite direct costs were equivalent, the cost due to the loss of labor productivity was higher in the PCI group (Int$ 4,511 (IQR: 18,062)/year vs Int$ 3,578 (IQR: 13,198)/year; p = 0.049], compared with CABG., Conclusions: Among young individuals with ACS and multivessel disease, surgical strategy was associated with a lower occurrence of MACE and lower indirect costs in the long-term., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alexim, Rocha, Dobri, Rosa Júnior, Reis, Nogueira, Soares, Sposito, de Paula and de Carvalho.)

Exosome-liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs.

Introduction: The aim of the study was to identify factors associated with the causes of in-hospital morbidity and mortality in an elderly Brazilian population due to osteoporotic hip fractures., Method: Retrospective cohort study involving a population over 60 years of age admitted to hospital due to osteoporotic hip fractures and followed up from hospitalization to outcome (discharge or mortality) from 2010 to 2018, in a public hospital in Brasília, the capital of Brazil. Multivariate analysis was performed using the Poisson regression model with a robust variance, observing the hierarchical model proposed and the receiver operating characteristic (ROC) curve to obtain the cutoff point for mortality incidence in relation the total length of hospital stay. Significance level was set as p < 0.05. The analyses were conducted using the SAS 9.4 software., Result: The mean hospital mortality rate among the 402 patients involved was 18.4%, and the associations made with the outcome mortality were per relevance: respiratory infection, age over 90 years, high preoperative cardiovascular risk, chronic obstructive pulmonary disease (COPD) as comorbidity, serum hemoglobin level ≤ 10 and other infections. Mortality also showed association with longer total length of hospital stay, as well as with prolonged postoperative period., Conclusion: Hip fractures in the elderly due to osteoporosis indicate a relationship between the sicker profile of the aging elderly population and the prevalence of chronic diseases strongly associated with in-hospital infections, contributing to increased mortality. There were fewer early interventions, and mortality was also associated with prolonged postoperative period. The aim of this study was not to compare independent variables with each other, but suggests the relationship between the presence of comorbidities, which predisposes to the development of infections, directly linked to mortality., Competing Interests: The authors have declared that no competing interests exist.

Objective: This article reports the range of motion, failure rate, and complications of patients with extensor mechanism injury after total knee arthroplasty (TKA) treated with extensor mechanism allograft with mid-term follow-up., Methods: Patients undergoing post-ATJ extensor mechanism transplantation from 2009 to 2018 were retrospectively evaluated. Demographics, the reason for transplantation, elapsed time from arthroplasty to transplantation, related surgical factors, immobilization time, range of motion, transplant failure, and complications were collected. The minimum follow-up was 24 months., Results: Twenty patients were evaluated. The mean follow-up was 70.8 +/- 33.6 months. The most common cause of extensor mechanism rupture was traumatic in 10 (50%) cases. Six patients underwent associated surgeries, one case of medial ligament complex reconstruction, and 5 cases of TKA revision. Eleven patients (55%) had transplant-related complications. The most common complication was an infection. Five cases presented transplant failure., Conclusion: Patients who underwent extensor mechanism allograft transplantation after total knee arthroplasty had a 25% failure rate with a mean follow-up of 6 years. Although there was no loss of flexion with the procedure and prolonged immobilization, the complication rate was not low. Level of evidence IV; case series ., Competing Interests: All authors declare no potential conflict of interest related to this article.

Purpose: We aimed to investigate the clinical and functional outcomes, including maximal and explosive strength, after chronic quadriceps tendon rupture repair with Modified Pulvertaft on Weave (MPW) technique METHODS: Knee joint range of motion (ROM), patella height, thigh circumference, and Lysholm and International Knee Documentation Committee (IKDC) scores were assessed preoperatively and postoperatively. The knee extensors maximal (isokinetic peak torque and isometric maximal voluntary contraction (MVC) torque) and explosive strength-rate of torque development (RTD) early [RTD 50 and RTD 100 ] and late [RTD 250 ]-were performed. We assessed the thigh circumference and vastus lateralis muscle thickness (MT) as indicators of quadriceps muscle mass, and the voluntary quadriceps activation using surface electromyography (EMG 50 )., Results: Nine patients (mean age: 53 ± 11 years) took part in the study. We observed a significant increase in the knee active ROM and a decreased extension deficit (both, P < .001), but not for pain (P = .07), IKDC (P = .07), and Lysholm (P = .21) after the surgery. We did not observe a difference between involved (n = 8) and uninvolved (n = 10) limbs for ROM, thigh circumference, and MT. We observed differences for extensors peak torque, MVC torque, and late RTD (all, P < .05). However, we did not observe differences for early RTD and EMG 50 . Significant positive correlations were observed for RTD 50 (ρ = .80) and RTD 100 (ρ = .81) vs EMG 50 . Both the IKDC and Lysholm were better correlated with the early than with later RTD., Conclusions: The MPW reestablished the active knee extension. The same level of quadriceps muscle mass was observed in both limbs, suggesting a lack of hypotrophy due to the injury. Although the involved limb had demonstrated lower knee extensors maximal strength, they demonstrate an equivalent early RTD when compared to the uninvolved limb. The early RTD seems to be better correlated with the patient's functionality than the later RTD and maximal strength., Level of Evidence: IV, case series., (Copyright © 2022 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective  The management of bone loss represents a challenge in revisions of total knee arthroplasty (rTKA) and in complex primary total knee arthroplasties (TKAs). The purpose of the present study was to evaluate the midterm outcomes (5-year minimum follow-up) of knee reconstructions with tantalum trabecular metal (TM) cones on bone defects Anderson Orthopaedics Research Institute (AORI) 2 and 3. Materials and Methods  A retrospective analysis of the medical records of patients operated on between July 2008 and November 2014 was performed, collecting the following data: age, gender, laterality, body mass index, etiology of arthrosis, comorbidities, AORI classification of bone defects, causes for revision, readmissions, reoperations, perioperative and postoperative complications, radiographic signs of osteointegration, and maintenance of the TM support. Results  A total of 11 patients with a mean follow-up of 7.28 years (standard deviation [SD] = 1.88; range = 5.12-10 years) was evaluated, with 1 patient operated upon for a primary arthroplasty, 6 for revision arthroplasties, and 4 for a second revision arthroplasty (re-revision). There were complications with the surgical wound, injury to the extensor mechanism and loosening of the femoral component in three of the patients that led to the necessity of four procedures due to complications with the surgical wound, injury to the extensor mechanism and loosening of the femoral component. Radiological signs of osteointegration of the trabecular cones were observed in all patients. We did not observe migration of the TM cones or the prosthetic components in the sample. Conclusion  The tantalum metaphyseal cones were able to provide efficient structural support to prosthetic implants with radiographic signs of osteointegration in the medium term., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Mesenchymal stromal cells (MSCs) have long been used in research for bone regeneration, with evidence of their beneficial properties. In the segmental area of MSC-based therapies, MSC-derived extracellular vesicles (EVs) have also shown great therapeutic effects in several diseases, including bone healing. This study aimed to assess whether the conditioning of MSCs improves the therapeutic effects of their derived extracellular vesicles for bone regeneration. Electronic research was performed until February 2021 to recover the studies in the following databases: PubMed, Scopus, and Web of Science. The studies were screened based on the inclusion criteria. Relevant information was extracted, including in vitro and in vivo experiments, and the animal studies were evaluated for risk of bias by the SYRCLE tool. A total of 463 studies were retrieved, and 18 studies met the inclusion criteria (10 studies for their in vitro analysis, and 8 studies for their in vitro and in vivo analysis). The conditioning methods reported included: osteogenic medium; dimethyloxalylglycine; dexamethasone; strontium-substituted calcium silicate; hypoxia; 3D mechanical microenvironment; and the overexpression of miR-375, bone morphogenetic protein-2, and mutant hypoxia-inducible factor-1α. The conditioning methods of MSCs in the reported studies generate exosomes able to significantly promote bone regeneration. However, heterogeneity regarding cell source, conditioning method, EV isolation and concentration, and defect model was observed among the studies. The different conditioning methods reported in this review do improve the therapeutic effects of MSC-derived EVs for bone regeneration, but they still need to be addressed in larger animal models for further clinical application.

Background: Brazil is a signatory to the World Health Organization End TB Strategy and the United Nations Sustainable Development Goals. This study aims to characterize tuberculosis (TB) deaths and TB mortality rates in Brazil for the period 1997-2017., Methods: We performed an ecological study based on information for TB deaths between 1997 and 2017 extracted from the Mortality Information System of the Brazilian Ministry of Health. Data included gender, age group and geographic regions. The trends in mortality rates were estimated using Joinpoint regression analysis, which identifies years in which there is a change in slope of the time series by the Monte Carlo permutation., Results: Between 1997 and 2017 there were 104 172 recorded TB deaths in Brazil and the mortality rates were higher for men and the elderly. The age-adjusted mortality rate decreased from 4.2 per 100 000 in 1997 to 3.0 per 100 000 in 2003 to 2.0 per 100 000 in 2017. The average percentage reduction from 1997 to 2003 was 6.2% (95% confidence interval [CI] -7.7 to -4.7) per year, while from 2003 to 2017 it was 3.0% (95% CI -3.4 to -2.5) per year, representing a slowdown in the rate of decline., Conclusion: The high number of deaths and the slowdown in the decline of mortality rates from TB in Brazil maintain the disease as an important public health concern and an obstacle to reaching goals set by international commitments., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data., Methods: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2)., Results: Higher IL-10 levels were observed in the case group compared to controls at T1 ( p = .006) and T2 ( p = .046). The IL-1β, IL-6 and TNF levels did not change during treatment in each group ( p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 ( p  < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed ( p = .048 and p = .004, respectively)., Conclusion: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

The study aimed to investigate the association between social capital indicators and depressive symptoms among university students from Brazil. The study drew on a sample of 579 randomly selected university students, from a greater crossnational study conducted in 2018. Students completed a self-administered questionnaire assessing depressive symptoms, indicators of social capital and lifestyle behaviors. Data were analyzed using multivariate logistic regression models. Indicators of social capital included trust, group membership and frequency of meeting friends. Four social capital indicators were significantly associated with clinically relevant depressive symptoms. Students who agreed that people are likely to take advantage of one another were more likely to report depressive clinically relevant symptoms (OR: 1.80, 95%CI: 1.00 - 3.23) as well as students who agreed that people are not willing to help in case needed (OR: 2.11, 95%CI: 1.02 - 4.36). Perceived stress, smoking and hazardous alcohol consumption were not associated with clinically relevant depressive symptoms. Social capital plays an important role in explaining depressive symptoms among Brazilian university students. The study suggests that creating trust and enhancing participation in social networks can be an important strategy for promoting mental health among university students investigated in this study.

Purpose: The aim of this study was to compare the fractal dimension (FD) measured at 2 bone sites (second cervical vertebra and mandible) on cone-beam computed tomography (CBCT). The research question was whether FD could serve as an accessory tool to refer postmenopausal women for densitometric analysis. Therefore, the reliability and accuracy of FD were evaluated., Materials and Methods: In total, 103 postmenopausal women were evaluated, of whom 52 had normal bone mineral density and 51 had osteoporosis, according to dual X-ray absorptiometry of the lumbar spine and hip. On the CBCT scans, 2 regions of interest were selected for FD analysis: 1 at the second cervical vertebra and 1 located at the mandible. The correlations between both measurements, intra- and inter-observer agreement, and the accuracy of the measurements were calculated. A P value less than 0.05 was considered to indicate statistical significance for all tests., Results: The mean FD values were significantly lower at the mandibular region of interest in osteoporotic patients than in individuals with normal bone mineral density. The areas under the curve were 0.644 ( P =0.008) and 0.531 ( P =0.720) for the mandibular and vertebral sites, respectively., Conclusion: FD at the vertebral site could not be used as an adjuvant tool to refer women for osteoporosis investigation. Although FD differed between women with normal BMD and osteoporosis at the mandibular site, it demonstrated low accuracy and reliability., Competing Interests: Conflicts of Interest: None, (Copyright © 2022 by Korean Academy of Oral and Maxillofacial Radiology.)

Osteoarthritis (OA) of the knee is highly prevalent and causes pain, stiffness, and harms the quality of life of millions of patients. Scientific evidence about radiofrequency ablation or rhizotomy of genicular nerves has been presented with increasing frequency in the literature for the treatment of chronic pain related to knee OA as an alternative to total knee arthroplasty. The main indication for this procedure is symptomatic OA unresponsive to conservative treatment, regardless of the disease evolution, although more common indications are in Kellgren-Lawrence grade III or IV, in post-total knee arthroplasty residual pain without an identified cause, in patients with comorbidities and high surgical risk, and those who do not want to undergo surgery. The aim of this study is to describe the step-by-step rhizotomy technique with pulsed radiofrequency of the 3 genicular nerves, guided by radioscopy and ultrasonography., (© 2021 The Authors.)

Post-transplantation cyclophosphamide (PTCy) reduces the incidence and severity of graft-versus-host disease (GVHD), thereby improving the safety and accessibility of allogeneic hematopoietic cell transplantation (HCT). We have shown that PTCy works by inducing functional impairment and suppression of alloreactive T cells. We also have identified that reduced proliferation of alloreactive CD4 + T cells at day +7 and preferential recovery of CD4 + CD25 + Foxp3 + regulatory T cells (T regs ) at day +21 are potential biomarkers associated with optimal PTCy dosing and timing in our B6C3F1→B6D2F1 MHC-haploidentical murine HCT model. To understand whether the effects of PTCy are unique and also to understand better the biology of GVHD prevention by PTCy, here we tested the relative impact of cyclophosphamide compared with five other optimally dosed chemotherapeutics (methotrexate, bendamustine, paclitaxel, vincristine, and cytarabine) that vary in mechanisms of action and drug resistance. Only cyclophosphamide, methotrexate, and cytarabine were effective in preventing fatal GVHD, but cyclophosphamide was superior in ameliorating both clinical and histopathological GVHD. Flow cytometric analyses of blood and spleens revealed that these three chemotherapeutics were distinct in constraining conventional T-cell numerical recovery and facilitating preferential T reg recovery at day +21. However, cyclophosphamide was unique in consistently reducing proliferation and expression of the activation marker CD25 by alloreactive CD4 + Foxp3 - conventional T cells at day +7. Furthermore, cyclophosphamide restrained the differentiation of alloreactive CD4 + Foxp3 - conventional T cells at both days +7 and +21, whereas methotrexate and cytarabine only restrained differentiation at day +7. No chemotherapeutic selectively eliminated alloreactive T cells. These data suggest that constrained alloreactive CD4 + Foxp3 - conventional T-cell numerical recovery and associated preferential CD4 + CD25 + Foxp3 + T reg reconstitution at day +21 may be potential biomarkers of effective GVHD prevention. Additionally, these results reveal that PTCy uniquely restrains alloreactive CD4 + Foxp3 - conventional T-cell proliferation and differentiation, which may explain the superior effects of PTCy in preventing GVHD. Further study is needed to determine whether these findings also hold true in clinical HCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hadjis, Nunes, Khan, Fletcher, Pohl, Venzon, Eckhaus and Kanakry.)

Perinatal mortality includes fetal mortality and early neonatal mortality (0 to 6 days of life). The study described perinatal deaths in Brazil in 2018 according to the modified Wigglesworth classification. The data sources were the Brazilian Mortality Information System and the Brazilian Information System on Live Births. Fetal mortality and perinatal mortality rates were calculated per 1,000 total births (live births plus stillbirths) and the early neonatal mortality rate per 1,000 live births, compared using their respective 95% confidence intervals (95%CI). Perinatal deaths were classified in groups of antepartum causes, congenital anomalies, prematurity, asphyxia, and specific causes. For each group of causes, the study calculated the number of deaths by weight group, in addition to mortality rates and respective 95%CI, besides the spatial distribution of mortality rates by state of Brazil. A total of 35,857 infant deaths were recorded, of which 18,866 (52.6%) were early neonatal deaths, while stillbirths totaled 27,009. Perinatal deaths totaled 45,875, for a mortality rate of 15.5‰ births. The highest mortality rate (7.6‰; 7.5‰-7.7‰) was observed in the antepartum group, followed by prematurity (3.6‰; 3.6‰-3.7‰). In the antepartum group, 14 of the 27 states (eight of which in the Northeast and four in the North) presented perinatal mortality rates above the national rate. Perinatal mortality in Brazil was high, and most deaths could have been prevented with investment in prenatal and childbirth care.

Objective: This study evaluates the association of serum retinol, hepcidin levels, and anemia in children., Methods: This cross-sectional study included 312 children, ages 6 to 59 mo, from Rio de Janeiro, Brazil. The association between hepcidin and retinol levels, hematologic parameters, and body mass index (BMI) was analyzed using a generalized linear model with and without adjustment for C-reactive protein (CRP) level. Logistic regression analysis was used to test anemia as an outcome and serum retinol level as a predictive variable using the odds ratio (OR) function., Results: Anemia was present in 14.6% of the children, 5.8% presented iron deficiency anemia, and 9.6% had vitamin A deficiency. The increase in serum retinol levels reduced the chances of anemia (OR = 0.13; confidence interval = 0.29-0.59). When CRP level was not adjusted for in the multiple regression analyses, retinol, ferritin levels, and BMI/age were predictors of serum hepcidin levels (β = -3.36, 0.14, 1.02, respectively; P = 0.032). Accordingly, serum retinol levels were inversely associated with CRP levels (β = -0.025 and P < 0.001)., Conclusions: The association between serum retinol and hepcidin levels in children ages 6 to 59 mo seems to be dependent on inflammation. Taken together, the results reinforce the need for the development of further studies to better understand the relationship between vitamin A and anemia of inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective  The present prospective, randomized and controlled study was conducted with 286 patients submitted to primary total knee arthroplasty (TKA) with the objective of evaluating the efficacy of the addition of antibiotics to bone cement as a way to prevent post arthroplasty infection (PAI). Methods  The patients were randomized into two groups: bone cement without antibiotic (No ATB, n  = 158) or cement with antibiotic (ATB, n  = 128), in which 2 g of vancomycin was added to 40 g of cement. The patients were followed up for 24 months after surgery. Results  Regarding preoperative demographic data, the distribution of patients between groups was homogeneous ( p  < 0.05). In the 24-month period, the overall infection rate was of 2.09% (6/286), with no difference (odds ratio [OR] = 1.636; 95% confidence interval [CI]: 0.294-9.080; p  = 0.694) between the ATB group (1.56%; 2/128) and the No ATB group (2.53%; 4/158). In the No ATB group, the infection was caused by methicillin-resistant Staphylococcus aureus (MRSA) ( n  = 2), methicillin-sensitive S. aureus (MSSA) ( n  = 1) and Eschirichia coli ( n  = 1). Proteus mirabilis and MSSA were isolated from patients in the ATB group. Among the comorbidities, all patients with PAI were hypertensive and nondiabetic. Two rheumatoid arthritis patients who developed PAI were from the ATB group. Conclusion  The use of cement with ATB reduced the absolute number of infections, but without statistical difference between the groups; thus, routine use should not be encouraged., Competing Interests: Conflito de interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives: Colostrum is the first secretion produced by the mammary glands and is present through the seventh day after birth. Colostrum has important immunomodulatory components and protective factors that contribute to the protection and development of newborns. The oropharyngeal administration of colostrum (OAC) has been proposed as a potential nutritional option for very low-birth-weight (VLBW) newborns (<1500 g). This study aimed to analyze the clinical outcomes of VLBW infants receiving OAC., Methods: This is a retrospective longitudinal study with nonprobability sampling of VLBW infants on the OAC protocol. VLBW infants for whom no OAC data were available, who received no dose, or who died within the first 7 d of life were excluded. The Mann-Whitney test was used to compare quantitative variables and the Wilcoxon test to assess the evolution of anthropometric values with a significance level of 5% (P < 0.05)., Results: Enteral nutritional therapy was commenced after 1 d (median: 1 d; interquartile range [IQR], 1-1 d). Full enteral feeding was achieved after 11 d (median: 11.0 d; IQR, 9.0-16.0 d). Birth weight was recovered after 11 d (median: 11 d; IQR, 7.0-14.0 d). OAC was commenced at 3 d of life, and 32.5 doses (IQR, 21.0-44.0 d) were given in total. There were significant differences in the evolution of anthropometric characteristics during hospitalization, with a tendency to recover birth weight more quickly the higher the number of doses administered (P = 0.07). Time to full enteral feeding was significantly longer and time to recovery of birth weight significantly shorter when OAC was commenced ≤3 d after birth (P = 0.023)., Conclusions: OAC was associated with a shorter time to recover birth weight and time to full enteral feeding., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives  The present paper aims to (1) verify the incidence and volume of blood transfusion among patients undergoing unilateral cemented total knee arthroplasty (TKA) in a single Brazilian reference center; (2) identify pre and perioperative variables to determine subjects with higher risk (i.e., predictive factors) for blood transfusion within 48 hours following surgery; (3) estimate the risk of blood transfusion during the first 48 hours after the procedure. Methods  The initial sample consisted of all patients undergoing TKA from August 2010 to August 2013. After applying the exclusion criteria, 234 patients aged 30 to 83 years old and diagnosed with primary or secondary osteoarthritis due to rheumatoid arthritis remained in the study. Results  Preoperative hemoglobin levels ≤ 12.3 g/dL and ischemia time ≥ 87 minutes were independent predictors for post-TKA blood transfusion, with a relative risk of 2.48 and 1.78, respectively. Approximately half of the TKA patients (51.3%) presenting these two variables required a blood transfusion. Conclusion  The incidence of post-TKA blood transfusion was 33.7%. On average, each transfused patient received 480 mL of packed red blood cells. Preoperative hemoglobin levels ≤ 12.3 g/dL ( p  < 0.001) and ischemia time ≥ 87 minutes ( p  < 0.047) were independent predictors for blood transfusion in TKA using a pneumatic cuff, with a relative risk of 2.48 and 1.78, respectively. Age, gender, diagnosis, or body mass index were not considered independent predictors for the need for blood transfusion up to 48 hours after the procedure., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The key to preventing early knee osteoarthritis is meniscal preservation. The main functions of the meniscus are impact absorption, mechanical load transmission, lubrication, joint stability, and proprioception. Radial lesions that extend to the joint capsule are called complete radial tears. This type of injury compromises 2 of the main meniscal functions, which are impact absorption and load distribution, which is equivalent, from a biomechanical perspective, to a total meniscectomy. In the recent past, the treatment of choice for this type of injury was partial meniscectomy. However, several studies have observed progressive joint degeneration after this type of treatment. Recently, different types of meniscal sutures involving radial lesions of the meniscus have been developed. It is believed that such repairs may bring a decrease in future osteoarthritis in this patient profile. The purpose of this article is to describe the steps of continuous meniscal suture for the treatment of radial tears of the medial and lateral menisci., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier.)

Orthopaedic surgeries by video arthroscopy have become increasingly popular, as they allow joint treatment through small incisions and minimal tissue damage. However, their execution requires specific skills from the surgeon, different from open surgery, which can only be achieved through practical training. These skills would be ideally performed on human cadaveric anatomical pieces which, however, can be difficult to access for different reasons. Animal anatomical models for surgical skills training have been used for years in medicine, and we observed that the bovine knee has anatomical characteristics quite similar to that of the human knee. In this study, we explain, step by step, the installation and creation of an arthroscopy laboratory with a bovine model, in an effort to contribute to several training centers in arthroscopic surgery around the world, assisting and guiding such centers to install arthroscopy laboratories and facilitating the improvement of more surgeons., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier.)

The medial meniscal root tear, a particular meniscal injury at the level of its posterior bone insertion, leads to a loss of impact absorption and load distribution capacity, similar to total meniscectomy. Therefore, its repair is fundamental for knee joint longevity. This type of injury often occurs in middle-aged patients with lower limbs varus malalignment, which results in mechanical overloading of the medial compartment and induces premature cartilage wear out. The success of meniscal root repair, with meniscal bone reinsertion, depends on the correction and realignment of varus deformities greater than 5° for physiological levels. In this situation, corrective tibial osteotomy combined with meniscal repair is indicated. Our goal is to describe the step-by-step technique of the valgus opening wedge tibial osteotomy combined with the arthroscopic reinsertion of the posterior meniscal root in tibia during the treatment of a patient with varus deformity and medial meniscus root tear., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier.)

The increase in the number of revision total knee arthroplasty surgeries has been observed in recent years, worldwide, for several causes. In the United States, a 601% increase in the number of total knee arthroplasties, between 2005 and 2030, is estimated. Among the enormous challenges of this complex surgery, the adequate treatment of bone defects is essential to obtain satisfactory and lasting results. The adequate treatment of bone defects aims to build a stable and lasting support platform for the implantation of the definitive prosthetic components and, if possible, with the reconstruction of bone stock. Concomitantly, it allows the correct alignment of the prosthetic and limb components, as well as restoring the height of the joint interline and, thus, restoring the tension of soft parts and load distribution to the host bone, generating a joint reconstruction with good function, stable, and painless. There are several options for the management of these bone defects, among them: bone cement with or without reinforcement with screws, modular metallic augmentations, impacted bone graft, structural homologous graft and, more recently, metal metaphyseal cones, and metaphyseal sleeves. The objective of the present article was to gather classic information and innovations about the main aspects related to the treatment of bone defects during revision surgeries for total knee arthroplasty., Competing Interests: Conflito de interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives:  The aim of this study is to evaluate the influence of different composite resin in the customization of glass fiber posts (GFPs) on bond strength and failure mode., Materials and Methods:  Thirty bovine roots were selected. The wall roots were reduced so that each wall had a minimum dentin thickness of 1 mm. Thirty GFPs were divided into three groups ( n = 10), which received different types of customization. The first had the GFP relined by bulk-fill flowable composite resin (BF), the second group had the GFP customized by conventional regular composite resin (CR), and the third group was cemented with dual resin cements (DRC), without relining. The root were sectioned, resulting in two 1.0-mm thick slices from cervical root regions only and push-out bond strength test was performed (EMIC, Universal testing machine). To determine failure mode, a stereomicroscope was used at ×40 magnification, with a 2.5D analysis., Statistical Analysis:  Data were analyzed using two-way ANOVA ( α = 0.05) and Tukey's test., Results:  BF (9.08 ± 1.9) and CR (9.17 ± 3.00) did not show a statistically significant difference ( p = 0.961), regarding the bond strength test values. However, there was a statistically significant difference between DRC (5.44 ± 1.89) and the others ( p < 0.05). BF (66.66%) and the CR group (47.61%) presented a predominantly failure mode type 6: mixed between resin cement and composite. While the highest failure index of the DRC group was type 2: adhesive between resin cement and dentin (47.61%)., Conclusion:  BF can be an alternative for the customization of fiber posts, since it presented a similar behavior to the established technique with conventional composites., Competing Interests: None declared., (European Journal of Dentistry. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Cardiovascular adverse events in patients with breast cancer undergoing chemotherapy (CT) are frequent due to the high cardiotoxic potential of treatments, especially doxorubicin (DOXO). This study aimed to evaluate the association of plasma levels of various biomarkers with cardiotoxicity in women with breast cancer on DOXO-based chemotherapy. In this single center prospective cohort, 80 breast cancer patients who used DOXO as a first-line treatment for cancer were evaluated. Patients were assessed at three time points: before CT (T0), 1 week after (T1) and 12 months after DOXO treatment (T2). The predominant histological classification was ductal carcinoma, n = 72 (90.0%); the most frequent molecular classification was Human epidermal growth factor receptor-type 2 positive (HER2+), n = 34 (43.0%). In patients submitted to complementary treatment with trastuzumab (n = 23), there was no association with cardio-specific biomarkers. Evaluating the clinical variables and the laboratory parameters in T1 and T2 in relation to T0, the reduction any time of N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), triglycerides and hematocrit levels showed an association with higher cardiotoxicity risk. In addition, increased levels of troponin I (cTnI) and glycated hemoglobin (HbA 1 c) showed an independent association with the occurrence of cardiotoxicity. These results suggest that the evaluation of these laboratory tests should be included routinely to identify breast cancer patients under DOXO treatment at cardiotoxicity risk.