Use of Plant Extracts in Polymeric Scaffolds in the Regeneration of Mandibular Injuries.

Severe loss of bone mass may require grafting, and, among the alternatives available, there are natural biomaterials that can act as scaffolds for the cell growth necessary for tissue regeneration. Collagen and elastin polymers are a good alternative due to their biomimetic properties of bone tissue, and their characteristics can be improved with the addition of polysaccharides such as chitosan and bioactive compounds such as jatoba resin and pomegranate extract due to their antigenic actions. The aim of this experimental protocol was to evaluate bone neoformation in experimentally made defects in the mandible of rats using polymeric scaffolds with plant extracts added. Thirty rats were divided into group 1, with a mandibular defect filled with a clot from the lesion and no graft implant (G1-C, n = 10); group 2, filled with collagen/chitosan/jatoba resin scaffolds (G2-CCJ, n = 10); and group 3, with collagen/nanohydroxyapatite/elastin/pomegranate extract scaffolds (G3-CHER, n = 10). Six weeks after surgery, the animals were euthanized and samples from the surgical areas were submitted to macroscopic, radiological, histological, and morphometric analysis of the mandibular lesion repair process. The results showed no inflammatory infiltrates in the surgical area, indicating good acceptance of the scaffolds in the microenvironment of the host area. In the control group (G1), there was a predominance of reactive connective tissue, while in the grafted groups (G2 and G3), there was bone formation from the margins of the lesion, but it was still insufficient for total bone repair of the defect within the experimental period standardized in this study. The histomorphometric analysis showed that the mean percentage of bone volume formed in the surgical area of groups G1, G2, and G3 was 17.17 ± 2.68, 27.45 ± 1.65, and 34.07 ± 0.64 (mean ± standard deviation), respectively. It can be concluded that these scaffolds with plant extracts added can be a viable alternative for bone repair, as they are easily manipulated, have a low production cost, and stimulate the formation of new bone by osteoconduction.

Mapping the learning styles of medical students in Brazil.

BACKGROUND: Medical education has evolved based on the application of pedagogical actions that place the student as the protagonist of the learning process through the use of active teaching methodologies. Within this context, higher education teachers should use strategies that focus on the student and his/her context and avoid traditional teaching methods. Specifically in medical schools, there is an even greater challenge since the teaching methods of medical curricula differ from those used in previous schooling. Consequently, students acquire their own style of processing information that is often incompatible with the profile of medical schools. This may be one of the factors responsible for the lack of motivation among undergraduates. OBJECTIVE: The aim of this study was to characterize the learning styles of students enrolled in a Brazilian medical school using the Felder-Soloman Index of Learning Styles (ILS). METHODS: This was a cross-sectional, descriptive, quantitative study that included students from the 1st to the 6th year of a Brazilian medical school. The students participating in this study voluntarily answered 44 questions about learning styles of the Felder-Silverman instrument validated in Brazil. The instrument was divided so that each domain consisted of 11 questions with two response options in which only one could be selected. For each domain, a score (1 point) was assigned to the selected option (a, b) of the question and the learning style category was determined as the difference between these values. For data collection and tabulation, we used the Learning Syle Platform (EdA Platform) developed based on Felder's studies since this system processes information about the dimension analyzed, the preferred style, and the most striking characteristics of each style. RESULTS: The results showed that sensing was the preferred learning style of the students, followed by the sequential and visual styles. It was not possible to determine whether gender or age influences the choice of learning methods because of the homogeneity of the results. CONCLUSIONS: The present data will enable teachers of the institution involved in this study to plan pedagogical actions that improve the students' self-awareness, as well as their teaching-learning skills, by choosing the most adequate active methodologies for the medical education programs considering the individuality of each student and class.

The quantum maxima for the basic graphs of exclusivity are not reachable in Bell scenarios.

A necessary condition for the probabilities of a set of events to exhibit Bell non-locality or Kochen-Specker contextuality is that the graph of exclusivity of the events contains induced odd cycles with five or more vertices, called odd holes, or their complements, called odd antiholes. From this perspective, events whose graph of exclusivity are odd holes or antiholes are the building blocks of contextuality. For any odd hole or antihole, any assignment of probabilities allowed by quantum theory can be achieved in specific contextuality scenarios. However, here we prove that, for any odd hole, the probabilities that attain the quantum maxima cannot be achieved in Bell scenarios. We also prove it for the simplest odd antiholes. This leads us to the conjecture that the quantum maxima for any of the building blocks cannot be achieved in Bell scenarios. This result sheds light on why the problem of whether a probability assignment is quantum is decidable, while whether a probability assignment within a given Bell scenario is quantum is, in general, undecidable. This also helps to understand why identifying principles for quantum correlations is simpler when we start by identifying principles for quantum sets of probabilities defined with no reference to specific scenarios. This article is part of the theme issue 'Quantum contextuality, causality and freedom of choice'.

On geometrical aspects of the graph approach to contextuality.

The connection between contextuality and graph theory has paved the way for numerous advancements in the field. One notable development is the realization that sets of probability distributions in many contextuality scenarios can be effectively described using well-established convex sets from graph theory. This geometric approach allows for a beautiful characterization of these sets. The application of geometry is not limited to the description of contextuality sets alone; it also plays a crucial role in defining contextuality quantifiers based on geometric distances. These quantifiers are particularly significant in the context of the resource theory of contextuality, which emerged following the recognition of contextuality as a valuable resource for quantum computation. In this paper, we provide a comprehensive review of the geometric aspects of contextuality. Additionally, we use this geometry to define several quantifiers, offering the advantage of applicability to other approaches to contextuality where previously defined quantifiers may not be suitable. This article is part of the theme issue 'Quantum contextuality, causality and freedom of choice'.

Viability of Collagen Matrix Grafts Associated with Nanohydroxyapatite and Elastin in Bone Repair in the Experimental Condition of Ovariectomy.

Bone lesions have the capacity for regeneration under normal conditions of the bone metabolism process. However, due to the increasing incidence of major traumas and diseases that cause bone-mineral deficiency, such as osteoporosis, scaffolds are needed that can assist in the bone regeneration process. Currently, natural polymeric scaffolds and bioactive nanoparticles stand out. Therefore, the objective of the study was to evaluate the osteoregenerative potential in tibiae of healthy and ovariectomized rats using mineralized collagen and nanohydroxyapatite (nHA) scaffolds associated with elastin. The in-vivo experimental study was performed with 60 20-week-old Wistar rats, distributed into non-ovariectomized (NO) and ovariectomized (O) groups, as follows: Controls (G1-NO-C and G4-O-C); Collagen with nHA scaffold (G2-NO-MSH and G5-O-MSH); and Collagen with nHA and elastin scaffold (G3-NO-MSHC and G6-O-MSHC). The animals were euthanized 6 weeks after surgery and the samples were analyzed by macroscopy, radiology, and histomorphometry. ANOVA and Tukey tests were performed with a 95% CI and a significance index of p < 0.05. In the histological analyses, it was possible to observe new bone formed with an organized and compact morphology that was rich in osteocytes and with maturity characteristics. This is compatible with osteoconductivity in both matrices (MSH and MSHC) in rats with normal conditions of bone metabolism and with gonadal deficiency. Furthermore, they demonstrated superior osteogenic potential when compared to control groups. There was no significant difference in the rate of new bone formation between the scaffolds. Ovariectomy did not exacerbate the immune response but negatively influenced the bone-defect repair process.

Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive 99mTc-labeling for SPECT imaging and radioguided surgery in prostate cancer.

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be -2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

Generalized Bell Scenarios: Disturbing Consequences on Local-Hidden-Variable Models.

Bell nonlocality and Kochen-Specker contextuality are among the main topics in the foundations of quantum theory. Both of them are related to stronger-than-classical correlations, with the former usually referring to spatially separated systems, while the latter considers a single system. In recent works, a unified framework for these phenomena was presented. This article reviews, expands, and obtains new results regarding this framework. Contextual and disturbing features inside the local models are explored, which allows for the definition of different local sets with a non-trivial relation among them. The relations between the set of quantum correlations and these local sets are also considered, and post-quantum local behaviours are found. Moreover, examples of correlations that are both local and non-contextual but such that these two classical features cannot be expressed by the same hidden variable model are shown. Extensions of the Fine-Abramsky-Brandenburger theorem are also discussed.

Impactos da pandemia de COVID-19 nas especialidades cirúrgicas em um hospital universitário da Bahia: um estudo transversal retrospectivo / Impacts of the COVID-19 pandemic on surgical specialties at a university hospital in Bahia: a retrospective cross-sectional study

Introdução: Desde o início da pandemia de COVID-19, as especialidades médicas adaptaram sua rotina, postergando procedimentos não essenciais, o que resultou em redução no número de atendimentos cirúrgicos, impactando diretamente nos hospitais de ensino. O objetivo desse trabalho é avaliar o impacto da pandemia de COVID-19 nas atividades das especialidades cirúrgicas do Hospital Universitário Professor Edgard Santos (C-HUPES), localizado em Salvador-BA. Método: Estudo observacional, transversal, retrospectivo, que compara o ano de 2020 ao ano de 2019, em que são analisados os impactos da pandemia nas atividades cirúrgicas (especialmente na cirurgia plástica) do hospital, através do número total de procedimentos, internações e de consultas ambulatoriais das especialidades cirúrgicas. Resultados: Redução de 45,45% no número total de procedimentos cirúrgicos foi observada, havendo um total de 220 cirurgias em 2019 e 120 cirurgias em 2020. Redução de 37,29% no número total de internamentos, total de 236 em 2019 e 148 em 2020. Observou-se diminuição de 40,90% nas consultas ambulatoriais, realizadas 2941 consultas em 2019 e 1738 consultas em 2020. Percebe-se que os piores períodos de redução em 2020 foram de março a junho, além de nova queda em novembro e dezembro. Conclusão: A pandemia impactou as atividades das especialidades cirúrgicas do C-HUPES, devido à redução total da quantidade de cirurgias, consultas e internamentos em 2020, prejudicando a assistência aos pacientes da cirurgia plástica em números absolutos. Infere-se que a pandemia de COVID-19 prejudicou a formação dos residentes de cirurgia plástica.

Introduction: Since the beginning of the COVID-19 pandemic, medical specialties have adapted their routine, postponing non-essential procedures, which resulted in a reduction in the number of surgical visits, directly impacting teaching hospitals. This work aims to evaluate the impact of the COVID-19 pandemic on the activities of the surgical specialties at the University Hospital Professor Edgard Santos (C-HUPES), located in Salvador-BA. Method: Observational, cross-sectional, retrospective study, which compares the year 2020 to the year 2019, in which the impacts of the pandemic on the surgical activities (especially plastic surgery) of the hospital are analyzed through the total number of procedures, hospitalizations, and outpatient consultations of surgical specialties. Results: A reduction of 45,45% of the total number of surgical procedures was observed, with 220 surgeries in 2019 and 120 surgeries in 2020. Reduction of 37.29% in hospitalizations, totaling 236 in 2019 and 148 in 2020. There was a decrease of 40.90% in outpatient consultations, with 2941 consultations performed in 2019 and 1738 consultations in 2020. It is noticed that the worst periods of reduction in 2020 were from March to June, in addition to a new drop in November and December. Conclusion: The pandemic impacted the activities of the surgical specialties at C-HUPES due to the total reduction in the number of surgeries, consultations, and hospitalizations in 2020, impairing the care of plastic surgery patients in absolute numbers. It is inferred that the COVID-19 pandemic hampered the training of plastic surgery residents.

Immunogenicity and reactogenicity of yellow fever vaccine in people with HIV.

OBJECTIVE: To evaluate immunogenicity and reactogenicity of yellow fever (YF) vaccine in people with HIV (PWH) compared to HIV-uninfected controls. DESIGN: In this longitudinal interventional trial (NCT03132311), PWH with CD4 + cell count ≥200 cells/µl and controls, aged 18-59, without a previous history of YF vaccination received a single standard dose of YF vaccine (17DD) and were followed at Days 5, 30 and Year 1. METHODS: YF-neutralization titers were measured at Days 0, 30 and Year 1 and geometric mean titers (GMT) were calculated. Adverse events (AE) and YF virus detection were measured at Days 5 and 30. Linear regression evaluated factors associated with YF-neutralization titers. RESULTS: Two hundred and eighteen PWH and 82 controls were included. At baseline, all PWH were using antiretroviral therapy; 92.6% had undetectable HIV viral load (VL) and median CD4 + cell count was 630 cells/µl [interquartile range (IQR) 463-888]. YF vaccine was safe and there were no serious AEs. At Day 30, seroconversion was observed in 98.6% of PWH [95% confidence interval (CI): 95.6-99.6] and in 100% of controls (95% CI: 93.9-100); at Year 1, 94.0% of PWH (95% CI: 89.6-96.7) and 98.4% of controls (95% CI 90.3-99.9) were seropositive. PWH had lower GMTs than controls at Day 30 and Year 1. Baseline VL >1000 copies/ml, low CD4 + cell count and low CD4 + /CD8 + ratio were associated with lower YF-neutralization titers. CONCLUSIONS: YF vaccine is safe in PWH with CD4 + cell count ≥200 cells/µl. YF vaccine immunogenicity is impaired in PWH, particularly among those with high VL, low CD4 + cell count and low CD4 + /CD8 + ratio at vaccination and YF-neutralization titers decays over time.

In Vivo Evaluation of Collagen and Chitosan Scaffold, Associated or Not with Stem Cells, in Bone Repair.

Natural polymers are increasingly being used in tissue engineering due to their ability to mimic the extracellular matrix and to act as a scaffold for cell growth, as well as their possible combination with other osteogenic factors, such as mesenchymal stem cells (MSCs) derived from dental pulp, in an attempt to enhance bone regeneration during the healing of a bone defect. Therefore, the aim of this study was to analyze the repair of mandibular defects filled with a new collagen/chitosan scaffold, seeded or not with MSCs derived from dental pulp. Twenty-eight rats were submitted to surgery for creation of a defect in the right mandibular ramus and divided into the following groups: G1 (control group; mandibular defect with clot); G2 (defect filled with dental pulp mesenchymal stem cells-DPSCs); G3 (defect filled with collagen/chitosan scaffold); and G4 (collagen/chitosan scaffold seeded with DPSCs). The analysis of the scaffold microstructure showed a homogenous material with an adequate percentage of porosity. Macroscopic and radiological examination of the defect area after 6 weeks post-surgery revealed the absence of complete repair, as well as absence of signs of infection, which could indicate rejection of the implants. Histomorphometric analysis of the mandibular defect area showed that bone formation occurred in a centripetal fashion, starting from the borders and progressing towards the center of the defect in all groups. Lower bone formation was observed in G1 when compared to the other groups and G2 exhibited greater osteoregenerative capacity, followed by G4 and G3. In conclusion, the scaffold used showed osteoconductivity, no foreign body reaction, malleability and ease of manipulation, but did not obtain promising results for association with DPSCs.

Influence of the Neuroprotective Properties of Quercetin on Regeneration and Functional Recovery of the Nervous System.

Quercetin is a dietary flavonoid present in vegetables, fruits, and beverages, such as onions, apples, broccoli, berries, citrus fruits, tea, and red wine. Flavonoids have antioxidant and anti-inflammatory effects, acting in the prevention of several diseases. Quercetin also has neuroprotective properties and may exert a beneficial effect on nervous tissue. In this literature review, we compiled in vivo studies that investigated the effect of quercetin on regeneration and functional recovery of the central and peripheral nervous system. In spinal cord injuries (SCI), quercetin administration favored axonal regeneration and recovery of locomotor capacity, significantly improving electrophysiological parameters. Quercetin reduced edema, neutrophil infiltration, cystic cavity formation, reactive oxygen species production, and pro-inflammatory cytokine synthesis, while favoring an increase in levels of anti-inflammatory cytokines, minimizing tissue damage in SCI models. In addition, the association of quercetin with mesenchymal stromal cells transplantation had a synergistic neuroprotective effect on spinal cord injury. Similarly, in sciatic nerve injuries, quercetin favored and accelerated sensory and motor recovery, reducing muscle atrophy. In these models, quercetin significantly inhibited oxidative stress and cell apoptosis, favoring Schwann cell proliferation and nerve fiber remyelination, thus promoting a significant increase in the number and diameter of myelinated fibers. Although there is still a lack of clinical research, in vivo studies have shown that quercetin contributed to the recovery of neurological functions, exerting a beneficial effect on the regeneration of the central and peripheral nervous system.

Collagen-chitosan-hydroxyapatite composite scaffolds for bone repair in ovariectomized rats.

Lesions with bone loss may require autologous grafts, which are considered the gold standard; however, natural or synthetic biomaterials are alternatives that can be used in clinical situations that require support for bone neoformation. Collagen and hydroxyapatite have been used for bone repair based on the concept of biomimetics, which can be combined with chitosan, forming a scaffold for cell adhesion and growth. However, osteoporosis caused by gonadal hormone deficiency can thus compromise the expected results of the osseointegration of scaffolds. The aim of this study was to investigate the osteoregenerative capacity of collagen (Co)/chitosan (Ch)/hydroxyapatite (Ha) scaffolds in rats with hormone deficiency caused by experimental bilateral ovariectomy. Forty-two rats were divided into non-ovariectomized (NO) and ovariectomized (O) groups, divided into three subgroups: control (empty defect) and two subgroups receiving collagen/chitosan/hydroxyapatite scaffolds prepared using different methods of hydroxyapatite incorporation, in situ (CoChHa1) and ex situ (CoChHa2). The defect areas were submitted to macroscopic, radiological, and histomorphometric analysis. No inflammatory processes were found in the tibial defect area that would indicate immune rejection of the scaffolds, thus confirming the biocompatibility of the biomaterials. Bone formation starting from the margins of the bone defect were observed in all rats, with a greater volume in the NO groups, particularly the group receiving CoChHa2. Less bone formation was found in the O subgroups when compared to the NO. In conclusion, collagen/chitosan/hydroxyapatite scaffolds stimulate bone growth in vivo but abnormal conditions of bone fragility caused by gonadal hormone deficiency may have delayed the bone repair process.

Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Topographic and Morphometric Study of the Foramen Spinosum of the Skull and Its Clinical Correlation.

Background and Objectives: The spinous foramen (FS) of the skull is an opening located in the greater wing of the sphenoid bone at the base of the skull, and it includes the middle meningeal vessels and the meningeal branch of the mandibular trigeminal nerve. The FS is commonly used as an anatomical landmark in neurosurgical procedures and neuroimaging of the middle cranial fossa because of its relationship with other cranial foramina and surrounding vascular and nervous structures. Thus, specific knowledge of its topography and possible anatomical variations is important regarding some surgical interventions and skull imaging. The aim of this study was to provide further details on the morphology of the FS of the skull by evaluating its topographic and morphometric relationships and correlating the findings with clinical practice. Materials and Methods: Thirty dried skulls of human skeletons from body donors from the collection of the Laboratory of Anatomical Microdissection at a medical school were used. The metric dimensions and variations of the FS and its relationship with adjacent bone structures were analyzed with an interface digital microscope. Results: The results showed the bilateral presence of the FS in all skulls; however, differences were observed in the shape, diameter, and topography in relation to the foramen ovale and the spine of the sphenoid. The FS was present in the greater wing of the sphenoid bone; however, in one skull, it was located in the lateral lamina of the pterygoid process. The FS was smaller than the foramen ovale. A round and oval FS shape was the most common (42.1% and 32.8% of the samples, respectively), followed by drop-shaped (12.5%) and irregular-shaped (12.5%) foramina. Conclusions: In conclusion, FS variations among individuals are common and must be considered by surgeons during skull base interventions in order to avoid accidents and postoperative complications.

Factors associated with long-term HIV pre-exposure prophylaxis engagement and adherence among transgender women in Brazil, Mexico and Peru: results from the ImPrEP study.

INTRODUCTION: The HIV epidemic continues to disproportionately impact Latin-American transgender women (TGW). We assessed factors associated with long-term pre-exposure prophylaxis (PrEP) engagement and adherence among TGW enrolled in the Implementation of PrEP (ImPrEP) study, the largest PrEP demonstration study in Latin America. METHODS: HIV-negative TGW aged ≥18 years reporting 1+eligibility criteria in the 6 months prior to enrolment (e.g. sex partner known to be living with HIV, condomless anal sex [CAS], transactional sex or having a sexually transmitted infection [STI]) who could safely take PrEP were enrolled. Follow-up visits were conducted at 4 weeks and then quarterly. We conducted logistic regression to identify factors associated with long-term PrEP engagement (3+ follow-up visits in 52 weeks) and complete self-reported adherence (no missed pills in the past 30 days) during follow-up. For both outcomes, we constructed multivariable models controlling for country, socio-demographics, sexual behaviour, substance use, STIs and self-reported adherence at 4 weeks (long-term engagement outcome only). RESULTS: From March 2018 to June 2021, ImPrEP screened 519 TGW, enrolled 494 (Brazil: 190, Mexico: 66 and Peru: 238) and followed them for 52 weeks. At baseline, 27.5% of TGW were aged 18-24 years, 67.8% were mixed-race and 31.6% had >secondary education. Most, 89.9% reported CAS, 61.9% had >10 sex partners and 71.9% reported transactional sex. HIV incidence was 1.82 cases per 100 person-years (95% confidence interval [CI]: 0.76-4.38). Almost half of TGW (48.6%) had long-term PrEP engagement, which was positively associated with reporting complete adherence at week 4 (aOR:2.94 [95%CI:1.88-4.63]) and was inversely associated with reporting CAS with unknown-HIV partner (aOR:0.52 [95%CI:0.34-0.81]), migration (aOR:0.54 [95%CI:0.34-0.84]), and being from Mexico (aOR:0.28 [95%CI:0.14-0.53]). Self-reported adherence was associated with TGW aged >34 (aOR:1.61 [95%CI:1.10-2.34]) compared to those aged 25-34 and those with >secondary education (aOR:1.55 [95%CI:1.10-2.19]) and was lower among TGW from Peru (aOR:0.29 [95%CI:0.21-0.41]) or reporting PrEP-related adverse effects (aOR:0.63 [95%CI:0.42-0.92]). CONCLUSIONS: Although TGW were willing to enrol in ImPrEP, long-term PrEP engagement and complete self-reported adherence were limited, and HIV incidence remained relatively high. A successful HIV prevention agenda should include trans-specific interventions supporting oral PrEP and exploring long-acting PrEP strategies for TGW.

Application of Fibrin Associated with Photobiomodulation as a Promising Strategy to Improve Regeneration in Tissue Engineering: A Systematic Review.

Fibrin, derived from proteins involved in blood clotting (fibrinogen and thrombin), is a biopolymer with different applications in the health area since it has hemostasis, biocompatible and three-dimensional physical structure properties, and can be used as scaffolds in tissue regeneration or drug delivery system for cells and/or growth factors. Fibrin alone or together with other biomaterials, has been indicated for use as a biological support to promote the regeneration of stem cells, bone, peripheral nerves, and other injured tissues. In its diversity of forms of application and constitution, there are platelet-rich fibrin (PRF), Leukocyte- and platelet-rich fibrin (L-PRF), fibrin glue or fibrin sealant, and hydrogels. In order to increase fibrin properties, adjuvant therapies can be combined to favor tissue repair, such as photobiomodulation (PBM), by low-level laser therapy (LLLT) or LEDs (Light Emitting Diode). Therefore, this systematic review aimed to evaluate the relationship between PBM and the use of fibrin compounds, referring to the results of previous studies published in PubMed/MEDLINE, Scopus and Web of Science databases. The descriptors "fibrin AND low-level laser therapy" and "fibrin AND photobiomodulation" were used, without restriction on publication time. The bibliographic search found 44 articles in PubMed/MEDLINE, of which 26 were excluded due to duplicity or being outside the eligibility criteria. We also found 40 articles in Web of Science and selected 1 article, 152 articles in Scopus and no article selected, totaling 19 articles for qualitative analysis. The fibrin type most used in combination with PBM was fibrin sealant, mainly heterologous, followed by PRF or L-PRF. In PBM, the gallium-aluminum-arsenide (GaAlAs) laser prevailed, with a wavelength of 830 nm, followed by 810 nm. Among the preclinical studies, the most researched association of fibrin and PBM was the use of fibrin sealants in bone or nerve injuries; in clinical studies, the association of PBM with medication-related treatments osteonecrosis of the jaw (MRONJ). Therefore, there is scientific evidence of the contribution of PBM on fibrin composites, constituting a supporting therapy that acts by stimulating cell activity, angiogenesis, osteoblast activation, axonal growth, anti-inflammatory and anti-edema action, increased collagen synthesis and its maturation, as well as biomolecules.

Duodenal Necrosis and Nonvariceal Digestive Bleeding After Terlipressin Administration for Treatment of Hepatorenal Syndrome: a Case Report of a Novel Side Effect of a Commonly Used Drug.

BACKGROUND: Terlipressin is widely used for treatment of hepatorenal syndrome and variceal bleeding in cirrhotic patients. However, it may be associated with side effects, especially those related to vasoconstriction, such as myocardial infarction or intestinal ischemia. This is a case report of a cirrhotic patient with nonvariceal upper gastrointestinal bleeding after duodenal necrosis due to the use of terlipressin, a novel side effect not yet described in literature to the best of our knowledge. CASE REPORT: A 51-year-old male patient, with alcoholic liver cirrhosis and hepatitis C virus infection, was admitted presenting oliguria associated with severe ascites and lower limb edema. His Model for End Stage Liver Disease-Sodium score was 19 and his serum creatine level was 2.12 mg/dL. Albumin infusion was performed for 48 hours, but his serum creatinine level reached 3.46 mg/dL. Terlipressin infusion was started in continuous infusion and serum creatinine levels progressively decreased. However, the patient presented hemorrhagic shock secondary to hematemesis after 7 days. Upper digestive endoscopy showed an extensive ulcerated lesion in the duodenal bulb, reaching 70% of its lumen, with hematic residues and necrotic foci. Terlipressin was suspended and proton pump inhibitors were started. Despite intensive care, the patient developed severe encephalopathy and reentrant seizures. He eventually died 10 days after the bleeding event. CONCLUSIONS: We described a case of nonvariceal upper gastrointestinal bleeding secondary to duodenal necrosis, which was caused by visceral ischemia induced by terlipressin. Given its fatality potential, this novel side effect should be remembered when using this medication in cirrhotic patients.

Suitability of Chitosan Scaffolds with Carbon Nanotubes for Bone Defects Treated with Photobiomodulation.

Biomaterials have been investigated as an alternative for the treatment of bone defects, such as chitosan/carbon nanotubes scaffolds, which allow cell proliferation. However, bone regeneration can be accelerated by electrotherapeutic resources that act on bone metabolism, such as low-level laser therapy (LLLT). Thus, this study evaluated the regeneration of bone lesions grafted with chitosan/carbon nanotubes scaffolds and associated with LLLT. For this, a defect (3 mm) was created in the femur of thirty rats, which were divided into 6 groups: Control (G1/Control), LLLT (G2/Laser), Chitosan/Carbon Nanotubes (G3/C+CNTs), Chitosan/Carbon Nanotubes with LLLT (G4/C+CNTs+L), Mineralized Chitosan/Carbon Nanotubes (G5/C+CNTsM) and Mineralized Chitosan/Carbon Nanotubes with LLLT (G6/C+CNTsM+L). After 5 weeks, the biocompatibility of the chitosan/carbon nanotubes scaffolds was observed, with the absence of inflammatory infiltrates and fibrotic tissue. Bone neoformation was denser, thicker and voluminous in G6/C+CNTsM+L. Histomorphometric analyses showed that the relative percentage and standard deviations (mean ± SD) of new bone formation in groups G1 to G6 were 59.93 ± 3.04a (G1/Control), 70.83 ± 1.21b (G2/Laser), 70.09 ± 4.31b (G3/C+CNTs), 81.6 ± 5.74c (G4/C+CNTs+L), 81.4 ± 4.57c (G5/C+CNTsM) and 91.3 ± 4.81d (G6/C+CNTsM+L), respectively, with G6 showing a significant difference in relation to the other groups (a ≠ b ≠ c ≠ d; p < 0.05). Immunohistochemistry also revealed good expression of osteocalcin (OC), osteopontin (OP) and vascular endothelial growth factor (VEGF). It was concluded that chitosan-based carbon nanotube materials combined with LLLT effectively stimulated the bone healing process.

Accuracy of 68Ga-PSMA PET-CT and PET-MRI in lymph node staging for localized prostate cancer.

OBJECTIVE: To evaluate the predictive value of positron emission computed tomography or magnetic resonance (PET-CT and PET-MRI) using gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA) in lymph node involvement in prostate cancer. METHODS: A retrospective study comprising 91 patients diagnosed with prostate cancer between 2016 to 2020, who underwent 68Ga-PSMA PET-CT or PET-MRI for staging before prostatectomy. The patients were divided into Group 1, with 65 patients with satisfactory pathological lymph node analysis, and Group 2, with 91 patients representing the sum of patients with pathological lymph node analysis and those with postoperative prostate-specific antigen within 60 days after surgery. Receiver Operating Characteristic curves were used to assess accuracy of predictive capacity of imaging exams for lymph node involvement. RESULTS: Regarding local clinical staging, the groups showed similar results, and 50% were classified as staging T2a. The accuracy of 68Ga-PSMA PET-CT for prostate cancer lymph node staging was 86.5% (95%CI 0.74-0.94; p=0.06), with a sensitivity of 58.3% and specificity of 95%. The accuracy of 68Ga-PSMA PET-MRI was 84.6% (95%CI 0.69-0.94; p=0.09), with a sensitivity of 40% and specificity of 100%. Considering both 68Ga-PSMA PET-CT and PET-MRI, the accuracy was 85.7% (95%CI 0.76-0.92; p=0.015), with sensitivity of 50% and specificity of 97%. CONCLUSION: The imaging tests 68Ga-PSMA PET-CT and PET-MRI were highly accurate to detect preoperative lymph node involvement, and could be useful tools to indicate the need for extended lymph node dissection during radical prostatectomy.

Experimental Evaluation of Chitosan Membrane and Collagen Sponge (TachoSil®) as Sealants in Cardiovascular Surgery.

INTRODUCTION: The objectives of this study are to experimentally evaluate the haemostatic effects of two organic substances, a membrane of chitosan and a collagen sponge coated with thrombin and human fibrinogen (TachoSil®), in sealing 7-0 needle stitches holes on the femoral arteries of rats as well as to evaluate local histological reactions. METHODS: Twenty-four rats were included, and four holes were made in each common femoral artery. In the control group, haemostasis was achieved only by compression with gauze sponge; and in the two other groups, haemostasis was achieved with application of one of these two substances. RESULTS: Membrane of chitosan and TachoSil® showed a power to reduce the time to achieve haemostasis compared with the control group (P=0.001), and the haemostatic effects of these two substances were comparable. There was lower blood loss in the groups where these two substances were used when compared with the control group, but no difference was found comparing the two substances. CONCLUSION: The use of these sealants did not promote more adhesion or local histological reactions when compared to the control group. Since chitosan is easy to find in nature, has a positive effect to promote haemostasis, and did not bring considerable local reactions, it might be used as a sealant in cardiovascular surgery.