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Objective: The objective of this study was to assess the existence of the obesity paradox in patients with COVID-19 admitted to the intensive care unit., Methods: This was a multicentric retrospective cohort study including individuals aged 18 years or older admitted to the intensive care unit with SARS-CoV-2. Data were obtained from electronic medical records. The primary outcome was in-hospital mortality. Multiple logistic regression and restricted cubic splines analyses were conducted to assess the association between BMI and mortality., Results: From March 2020 to December 2021, 977 patients met the inclusion criteria, and 868 were included in the analysis. Obesity was identified in 382 patients (44%). Patients with obesity more often underwent prone positioning (42% vs. 28%; p < 0.001), although they used less vasoactive medications (57% vs. 68%; p < 0.001). The overall in-hospital mortality was 48%, with 44% observed in the subgroup of individuals with obesity and 50% in those without obesity (p = 0.06). Patients with BMI < 25 kg/m 2 had the highest mortality., Conclusions: Obesity was not associated with higher mortality rates in critically ill patients with COVID-19. Moreover, patients with BMI < 25 kg/m 2 had a higher mortality rate compared with those in higher BMI categories., (© 2024 The Obesity Society.)

Cell-membrane hybrid nanoparticles (NPs) are designed to improve drug delivery, thermal therapy, and immunotherapy for several diseases. Here, we report the development of distinct biomimetic magnetic nanocarriers containing magnetic nanoparticles encapsulated in vesicles and IR780 near-infrared dyes incorporated in the membranes. Distinct cell membranes are investigated, red blood cell (RBC), melanoma (B16F10), and glioblastoma (GL261). Hybrid nanocarriers containing synthetic lipids and a cell membrane are designed. The biomedical applications of several systems are compared. The inorganic nanoparticle consisted of Mn-ferrite nanoparticles with a core diameter of 15 ± 4 nm. TEM images show many multicore nanostructures (∼40 nm), which correlate with the hydrodynamic size. Ultrahigh transverse relaxivity values are reported for the magnetic NPs, 746 mM -1 s -1 , decreasing respectively to 445 mM -1 s -1 and 278 mM -1 s -1 for the B16F10 and GL261 hybrid vesicles. The ratio of relaxivities r 2 / r 1 decreased with the higher encapsulation of NPs and increased for the biomimetic liposomes. Therapeutic temperatures are achieved by both, magnetic nanoparticle hyperthermia and photothermal therapy. Photothermal conversion efficiency ∼25-30% are reported. Cell culture revealed lower wrapping times for the biomimetic vesicles. In vivo experiments with distinct routes of nanoparticle administration were investigated. Intratumoral injection proved the nanoparticle-mediated PTT efficiency. MRI and near-infrared images showed that the nanoparticles accumulate in the tumor after intravenous or intraperitoneal administration. Both routes benefit from MRI-guided PTT and demonstrate the multimodal theranostic applications for cancer therapy.

In this technical report study, we describe technique for performing the osteotomy and screw passage in minimally invasive fourth-generation hallux valgus surgery with transverse and akin extra-articular metaphyseal osteotomy (META) using a 3D-printed patient-specific surgical instrumentation guide. In an effort to minimize the learning curve and address the variability associated with technical corrections and screw placement, we have initiated the creation of personalized patient-specific instrumentation guides using 3D printing. Our hypothesis is that this approach will enhance safety, precision, decrease surgical time, and reduce exposure to radiation. Level of Evidence: Level V, expert opinion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although several studies indicate the harmful effects of bleaching on pulp tissue, the demand for this procedure using high concentrations of hydrogen peroxide (HP) is high., Objectives: To investigate the influence of bleaching on the pulp tissue., Methods: Electronic searches were conducted (PubMed/MEDLINE, Scopus, Cochrane Library and grey literature) until February 2021. Only in vivo studies that evaluated the effects of HP and/or carbamide peroxide (CP) bleaching gels on the inflammatory response in the pulp tissue compared with a non-bleached group were included. Risk of bias was performed according to a modified Methodological Index for Non-Randomized Studies scale for human studies and the Systematic Review Centre for Laboratory Animal Experimentation's RoB tool for animal studies. Meta-analysis was unfeasible., Results: Of the 1311 studies, 30 were eligible. Of these, 18 studies evaluated the inflammatory response in animal models. All these studies reported a moderate-to-strong inflammatory response in the superficial regions of pulp, characterized by cell disorganization and necrotic areas, particularly during the initial periods following exposure to 35%-38% HP, for 30-40 min. In the evaluation of human teeth across 11 studies, seven investigated inflammatory responses, with five observing significant inflammation in the pulp of bleached teeth. In terms of tertiary dentine deposition, 11 out of 12 studies noted its occurrence after bleaching with 35%-38% HP in long-term assessments. Additionally, three studies reported significant levels of osteocalcin/osteopontin at 2 or 10 days post-treatment. Other studies indicated an increase in pro-inflammatory cytokines ranging from immediately up to 10 days after bleaching. Studies using humans' teeth had a low risk of bias, whereas animal studies had a high risk of bias., Discussion: Despite the heterogeneity in bleaching protocols among studies, High-concentrations of HP shows the potential to induce significant pulp damage., Conclusions: High-concentrations of bleaching gel increases inflammatory response and necrosis in the pulp tissue at short periods after bleaching, mainly in rat molars and in human incisors, in addition to greater hard tissue deposition over time. However, further well-described histological studies with long-term follow-up are encouraged due to the methodological limitations of these studies., Registration: PROSPERO (CRD42021230937)., (© 2024 British Endodontic Society. Published by John Wiley & Sons Ltd.)

The Program of Education through Work for Health (PET-Health), with a focus on interprofessionality, is one of the actions of the Plan for the Strengthening of Interprofessional Education in Brazil. This research aimed to systematically analyze the characteristics of the proposals submitted to the public notice of the PET-Health Interprofessionality specifically in relation to the theoretical-conceptual and methodological alignment of interprofessional education (IPE). The study is a qualitative document content analysis. We analyzed one hundred and twenty projects submitted to the selection process from institutions participating in the PET-Health Interprofessionality. Content analysis followed three steps: pre-analysis, exploration of the material, and treatment and interpretation of results. Seven categories were identified: a) alignment with the theoretical-conceptual frameworks of IPE, b) curriculum changes, c) faculty development with a focus on IPE, d) articulation among objectives, actions, and results expected related to IPE, e) strategies for monitoring and evaluation, f) involvement of users/families and community, and g) development of collaborative competencies. We conclude that while some advancements have been made, there remains a need for more in-depth discussion in Brazil to ensure the development of competencies capable of assuring more integral, resolute, and safer healthcare services, with capacity to (re)signify user-centered care in the planning and delivery of healthcare.

Background: Recognizing preoperative first-ray hypermobility is important to planning hallux valgus (HV) surgery. A recent study showed the minimally invasive chevron Akin (MICA) osteotomy increased varus displacement of the proximal fragment of the first metatarsal osteotomy. The present study aims to evaluate the ability of the radiographic first-ray squeeze test to predict the varus displacement of the proximal fragment of the first metatarsal osteotomy when performing the MICA procedure., Methods: A prospective case series of patients with moderate to severe HV who underwent MICA was performed. The HV deformity correction was analyzed by comparing the preoperative and 12-week postoperative hallux valgus angle (HVA) and the intermetatarsal angle between the first and second rays (1-2 IMA). The ability of the radiographic first-ray squeeze test to predict the varus displacement of the first metatarsal was done by comparing the preoperative 1-2 IMA measured in the AP radiographic first-ray squeeze test (IMA-ST) with the intermetatarsal angle between the second metatarsal and the axis of the first metatarsal osteotomy proximal fragment (IAPF) taken 12 weeks postoperatively., Results: Between July 2022 and May 2023, a total of 39 feet in 28 patients underwent MICA. The mean IMA improved from 13.8 (SD = 2.2) to 3.8 degrees (SD = 1.5) ( P  < .001), and the mean HVA improved from 27.8 (SD = 6.1) to 4.9 degrees (SD = 2.5) ( P  < .001). A linear regression analysis revealed that IMA-ST is highly associated with the 12 week assessed IAPF ( P  < .001)., Conclusion: The preoperative radiographic first-ray squeeze test appears to predict with high fidelity the varus displacement of the proximal fragment of the first metatarsal that can occur after the MICA procedure. Level of Evidence : Level III, prospective cohort study., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

The Program of Education through Work - Health (PET-Health) Interprofessionality is one of the strategic actions of the "Plan for the Strengthening of Interprofessionality" in healthcare in Brazil. Based on the experience of the program, this paperexamines the aspects that impact the adoption and strengthening of interprofessional education and collaborative practices, and issues recommendations for the strengthening of interprofessionality as a guiding principle of training and working in healthcare. This is a document analysis of partial reports from the six- and 12-months of execution of 120 PET-Health Interprofessionality projects in Brazil. The data were analyzed based on content analysis and the categories elaborated a priori. The aspects that impact the adoption and strengthening of interprofessionality in training and working in healthcare, and future recommendations, were organized in the relational, processual, organizational, and contextual dimensions, according to the framework by Reeves et al. The PET-Health Interprofessionality expanded the understanding of elements of interprofessional education and practice and showed that the discussion must take on a more political, critical, and reflexive character. The analysis points to the need for continuity of teaching-learning activities as a strategy to foster interprofessional capacity in healthcare services and consequent strengthening of the Unified Healthcare System in Brazil.

Background: Several operative procedures have been described for treating a Kim lesion. However, no physical therapy intervention has been documented as conservative treatment for these cases., Objective: The purpose of this report was to describe a physical therapy management protocol for an athlete with a Kim lesion., Case Description: A 22-year-old female volleyball athlete presented to physical therapy with an 8-month history of right shoulder pain when performing the serve and attack sports gestures. Pain was 5/10 on the visual analogue scale (VAS). Pain was localized along the glenohumeral joint, around the long head of the biceps brachii tendon, and at the subscapularis tendon insertion. Shoulder range of motion (ROM) was limited to flexion (150°), abduction (158°), and internal rotation (80°). Kim lesion was confirmed by clinical tests (Kim test and Jerk test) and via magnetic resonance imaging. Shoulder functional outcomes were verified through the University of California Los Angeles (UCLA) shoulder rating scale. Upper extremity sensorimotor control was verified in bimanual support by stabilometry on a baropodometer. Core function was assessed through a plank test and a side plank test. The 8-week course of treatment included manual therapy, physical agents, shoulder and scapular mobilizations, resistance and sensorimotor exercises, core strengthening, and functional exercises., Outcomes: Physical therapy interventions resulted in a decrease in VAS pain (3/10), an increase in shoulder ROM (10.8°) and in UCLA shoulder score (from 22 to 33 points), a reduction in the center of pressure displacement (27-56%), and an increase in plank test (45%) and side plank test (21-29%) performance. The athlete had a full return to sport after the treatment., Conclusion: We concluded that the protocol used for conservative management of Kim lesion resulted in clinical satisfactory physical and functional outcomes for the athlete.

Purpose: To evaluate the frequency of rapid response team (RRT) calls by time of day and their association with in-hospital mortality., Materials and Methods: This was a retrospective cohort study of all RRT calls at a tertiary teaching hospital in Porto Alegre, Brazil. Patients were categorized according to the time of initial RRT activation. Activations were classified as daytime (7:00-18:59) or nighttime (19:00-6:59). The primary outcome was in-hospital mortality rate. The secondary outcome was ICU admission within 48 h of RRT assessment., Results: During the study period, 4522 patients were included in the final analysis. Cardiovascular and respiratory changes were more common causes of nighttime activation, whereas neurological and laboratory changes were more common during the daytime. The in-hospital mortality rate was 23.9% (1081/4522). Nighttime RRT calls were not associated with worse outcomes than daytime calls. However, a decrease in the number of calls was observed during nursing handover periods (7:00, 13:00 and 19:00). Two time periods were associated with increased adjusted odds for mortality: 12:00-13:00 (adjusted OR 2.277; 95% CI 1.392-3.725) and 19:00-20:00 (adjusted OR 1.873; CI 1.873; 95% 1.099-3.190)., Conclusion: We found that nighttime RRT calls were not associated with worse outcomes than daytime RRT calls. However, a decrease in the number of calls and higher mortality was observed during nursing handover periods., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Salmonella Typhimurium is an important agent of foodborne diseases. In Peru, the emergence of multidrug-resistant isolates of S. Typhimurium from the food chain could be linked to guinea pig farming as a potential reservoir and their uncontrolled antibiotic treatment against salmonellosis. In this study, we performed the sequencing, genomic diversity, and characterization of resistance elements transmitted by isolates from farm and meat guinea pigs. The genomic diversity and antimicrobial resistance of S. Typhimurium isolates were performed using nucleotide similarity, cgMLST, serotyping, phylogenomic analyses, and characterization of resistance plasmids. We found at least four populations of isolates from farm guinea pigs and four populations from meat guinea pigs without finding isolated transmission between both resources. Genotypic resistance to antibiotics was observed in at least 50% of the isolates. Among the farm guinea pig isolates, ten were found to be resistant to nalidixic acid, and two isolates exhibited multidrug resistance to aminoglycosides, tetracycline-fluoroquinolone (carrying strA-strB-tetA-tetB genes and gyrA S83F mutation), or trimethoprim-sulfonamide (carrying AaadA1-drfA15-sul1 genes). Additionally, two isolates from the meat source were resistant to fluoroquinolones (one of which had enrofloxacin resistance). The transmissible resistance plasmids with insertion sequences (IS) such as IncI-gamma-K1-ISE3-IS6, IncI1-I (alpha)-IS21-Tn10, and Col (pHAD28) were commonly found in isolates belonging to the HC100-9757 cluster from both guinea pigs and human hosts. Altogether, our work provides resistance determinants profiles and Salmonella sp. circulating lineages using WGS data that can promote better sanitary control and adequate antimicrobial prescription., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Study Objective: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist used for management of type 2 diabetes and/or obesity. To test the hypothesis that perioperative semaglutide use is associated with delayed gastric emptying and increased residual gastric content (RGC) despite adequate preoperative fasting, we compared the RGC of patients who had and had not taken semaglutide prior to elective esophagogastroduodenoscopy. The primary outcome was the presence of increased RGC., Design: Single-center retrospective electronic chart review., Setting: Tertiary hospital., Patients: Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021-March/2022., Interventions: Patients were divided into two (SG = semaglutide, NSG = non-semaglutide) groups, according to whether they had received semaglutide within 30 days prior to the esophagogastroduodenoscopy., Measurements: Increased RGC was defined as any amount of solid content, or > 0.8 mL/Kg (measured from the aspiration/suction canister) of fluid content., Main Results: Of the 886 esophagogastroduodenoscopies performed, 404 (33 in the SG and 371 in the NSG) were included in the final analysis. Increased RGC was observed in 27 (6.7%) patients, being 8 (24.2%) in the SG and 19 (5.1%) in the NSG (p < 0.001). Semaglutide use [5.15 (95%CI 1.92-12.92)] and the presence of preoperative digestive symptoms (nausea/vomiting, dyspepsia, abdominal distension) [3.56 (95%CI 2.2-5.78)] were associated with increased RGC in the propensity weighted analysis. Conversely, a protective [0.25 (95%CI 0.16-0.39)] effect against increased RGC was observed in patients undergoing esophagogastroduodenoscopy combined with colonoscopy. In the SG, the mean time of preoperative semaglutide interruption in patients with and without increased RGC was 10.5 ± 5.5 and 10.2 ± 5.6 days, respectively (p = 0.54). There was no relationship between semaglutide use and the amount/volume of RGC found on esophagogastroduodenoscopy (p = 0.99). Only one case (in the SG) of pulmonary aspiration was reported., Conclusions: Semaglutide was associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Digestive symptoms prior to esophagogastroduodenoscopy were also predictive of increased RGC., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Zika virus (ZIKV) infection became a global public health concern, causing an epidemic in Latin America from 2015 to 2016, when a sudden increase in cases of microcephaly and other congenital anomalies was observed. In 2016, the Centers for Disease Control and Prevention and the World Health Organization defined congenital Zika-associated syndrome (CZS) as a set of congenital anomalies seen in children born to mothers with a history of gestational Zika fever, who have microcephaly as the most prevalent clinical sign. In order to describe the magnitude of CZS in Brazil, this study estimated the burden of disease due to CZS in Brazil using the disability-adjusted life years (DALY) indicator and other frequency measures, such as incidence and mortality rate, during the years 2015-2020. The association of these indicators with socioeconomic variables was also evaluated using Spearman's correlation coefficient. Choropleth maps were used to evaluate the spatial distribution of the indicators evaluated and the spatial autocorrelation was verified by the Bivariate Moran Local Index. From 2015 to 2020, 3,591 cases of CZS were confirmed in Brazil, with an incidence of 44.03 cases per 1000 live births, and a specific mortality of 12.35 deaths per 1000 live births. A global loss of 30,027.44 DALYs was estimated from 2015 to 2020. The Northeast region had the highest values for all health indicators assessed. Spatial correlation and autocorrelation analyses showed significant associations between health and socioeconomic indicators, such as per capita income, Gini index, illiteracy rate and basic sanitation. The study allowed us to have access to all reported cases of CZS, showing us the possible situation of the disease in Brazil; therefore, we believe that our results can help in the understanding of future studies., (© 2023. The Author(s).)

Although well-established and adopted by commercial laboratories, the in vitro embryo production system still requires refinements to achieve its highest efficiency. Early embryonic development is a dynamic event, demanding suitable conditions to provide a high number of embryos with quality and competence. The first step to obtaining an optimized in vitro environment is to know the embryonic metabolism and energy request throughout the different stages of development. Oxygen plays a crucial role in several key biological processes necessary to sustain and complete embryonic development. Nonetheless, there is still controversy regarding the optimal in vitro atmospheric concentrations during culture. Herein, we discuss the impact of oxygen tension on the viability of in vitro-produced embryos during early development. The importance of oxygen tension is addressed as its roles regarding essential embryonic traits, including embryo production rates, embryonic cell viability, gene expression profile, epigenetic regulation, and post-cryopreservation survival. Finally, we highlight the damage caused by in vitro unbalanced oxygen tensions and strategies to mitigate the harmful effects.

Introduction: Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood., Objective: In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children., Methods: Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns., Results: Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein., Conclusion: Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection., 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 © 2023 Moragas, Alves, Oliveira, Salomão, Azevedo, da Silva, Basílio-de-Oliveira, Basílio-de-Oliveira, Mohana-Borges, de Carvalho, Rosman, Paes and Rabelo.)

Objective: Pronation of the first metatarsal in hallux valgus has recently been discussed among foot and ankle surgeons. This study aimed to evaluate the potential radiographic correction of moderate and severe hallux valgus using the percutaneous Chevron and Akin (PECA) technique., Methods: We evaluated 45 feet in 38 patients (mean age 65.3 years old [36 - 83]; 4 men; 34 women; 7 bilateral) who underwent surgical correction using the PECA technique. The radiographic images evaluated were anteroposterior radiographs obtained pre- and postoperatively at least 6 months after surgery, including the metatarsophalangeal angle, the intermetatarsal angle, pronation of the first metatarsal, displacement of the distal fragment, medial sesamoid position and bone union., Results: All parameters evaluated showed significant postoperative improvement, including correction of pronation of the first metatarsal (p < .05) and position of the sesamoid (p < .05). There was a union of osteotomies in all feet. No complications were observed, such as screw loosening or necrosis of the first metatarsal head., Conclusion: The PECA technique can correct pronation of the first metatarsal in moderate and severe hallux valgus, and other deformity-associated parameters. Level of Evidence IV; Case Series., Competing Interests: All authors declare no potential conflict of interest related to this article.

Backcground & Aims: There in no data regarding outcomes after hospital discharge for underweight critically ill patients. This study aimed to assess long-term survival and functional capacity in underweight critically ill patients., Materials & Methods: Prospective observational study that included underweight critically ill patients (BMI <20 kg/cm 2 ) followed-up one year after hospital discharge. To assess functional capacity, we interviewed patients or caregivers and performed Katz index (KI) and Lawton scale. Patients were divided into two groups: (1) poor functional capacity, if the patient had less points than the median of the Katz and IADL score, and (2) good functional capacity, if at least one score was above the median. Extremely low weight defined as less than 45 kg., Results: We assessed the vital status of 103 patients. Mortality was 38.8% (median 362 [136, 422] days of follow-up). We interviewed 62 patients or proxies. No difference was observed between survivors and non-survivors regarding weight and BMI at intensive care unit admission and nutritional therapy received in the first days of intensive care admission. Patients with poor functional capacity had lower admission weight (43.9 vs 52 ± 7.9 kg, p < 0.001) and BMI (17 ± 2.1 vs 18.2 ± 1.8 kg/cm 2 , p = 0.028). In a multivariate logistic regression, weight under 45 kg was independently associated with poor functional capacity (OR = 13.6, 95%CI, 3.7 to 66.5) CONCLUSION: Underweight critically ill patients have high mortality and a persistent functional impairment, the last being more important in extremely low weight., Clinical Trial Registry: ClinicalTrials.gov number NCT03398343., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

A wide-ranging review study regarding the molecular characterization of the first cell lineages of the developmental embryo is lacking, especially for the primary events during earliest differentiation which leads to the determination of cellular fate. Here, a systematic review and meta-analysis were conducted according to PRISMA guidelines. MEDLINE-PubMed was searched based on an established search strategy through April 2021. Thirty-six studies fulfilling the inclusion criteria were subjected to qualitative and quantitative analysis. Among the studies, 50 % (18/36) used mice as an animal model, 22.2 % (8/36) pigs, 16.7 % (6/36) cattle, 5.5 % (2/36) humans, and 2.8 % (1/36) goats as well as 2.8 % (1/36) equine. Our results demonstrated that each of the first cell lineages of embryos requires a certain pattern of expression to establish the cellular determination of fate. Moreover, these patterns are shared by many species, particularly for those molecules that have already been identified in the literature as biomarkers. In conclusion, the present study integrated carefully chosen studies regarding embryonic development and first cellular decisions in mammalian species and summarized the information about the differential characterization of the first cell lineages and their possible relationship with specific gene expression., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females., Methods: In 51 critically ill ICU patients (26 males, 15 females) and 49 healthy controls (36 males and 27 females), we assessed their general and disease characteristics and collected arterial(ized) blood in the postabsorptive state after pulse administration of 8 ml of a solution containing 18 stable AA tracers. In contrast to the original study, we now fitted the decay curves and calculated non-compartmental whole body amino acid production (WBP) and compartmental measurements of metabolism, including intracellular amino acid production. We measured amino acid enrichments and concentrations by LC-MS/MS and derived statistics using AN(C)OVA., Results: Critically ill males and females showed an increase in the WBP of many amino acids, including those related to protein breakdown, but females showed greater elevations, or in the event of a reduction, attenuated reductions. Protein breakdown-independent WBP differences remained between males and females, notably increased glutamine and glutamate WBP. Only severely ill females showed a lower increase in WBP of many amino acids in comparison to moderately ill females, suggesting a suppressed metabolism. Compartmental analysis supported the observations., Conclusions: The present study shows that females have a different response to critical illness in the production of several amino acids and changes in protein breakdown, observations made possible using our innovative stable tracer pulse approach., Clinical Trial Registry: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365)., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality., Methods: This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use., Results: We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24-1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21-1.78)., Conclusions: Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality., (© 2023. The Author(s).)

Objective: Calotropis procera latex protein (CpLP) is a popular anti-inflammatory and therefore we aimed to study its effects on inflammatory bone loss., Design: Male Wistar rats were subjected to a ligature of molars. Groups of rats received intraperitoneally CpLP (0.3 mg/kg, 1 mg/kg, or 3 mg/kg) or saline (0.9% NaCl) one hour before ligature and then daily up to 11 days, compared to naïve. Gingiva was evaluated by myeloperoxidase activity and interleukin-1 beta (IL-1β) expression by ELISA. Bone resorption was evaluated in the region between the cement-enamel junction and the alveolar bone crest. The histology considered alveolar bone resorption and cementum integrity, leukocyte infiltration, and attachment level, followed by immunohistochemistry bone markers between 1 st and 2 nd molars. Systemically, the weight of the body and organs, and a leukogram were performed., Results: The periodontitis significantly increased myeloperoxidase activity and the IL-1β level. The increased bone resorption was histologically corroborated by periodontal destruction, leukocyte influx, and attachment loss, as well as the increasing receptor activator of the nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio, and Tartrate-resistant acid phosphatase (TRAP)+ cells when compared to naïve. CpLP significantly reduced myeloperoxidase activity, level of IL-1β, alveolar bone resorption, periodontal destruction, leukocyte influx, and attachment loss. The CpLp also reduced the RANKL/OPG ratio and TRAP+ cells, when compared with the saline group, and did not affect the systemic parameters., Conclusions: CpLP exhibited a periodontal protective effect by reducing inflammation and restricting osteoclastic alveolar bone resorption in this rat model., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: β-hydroxy-β-methylbutyrate (HMB) might improve muscle function and maintain its mass in critically ill patients. We aimed to investigate whether the administration of HMB influenced the plasma levels of growth hormone (GH)/insulin-like growth factor-1 (IGF-1), C-peptide, and 25-OH vitamin-D., Methods: Post-hoc analysis of the study HMB-ICU, a randomized, placebo-controlled double-blind trial., Inclusion Criteria: Intensive care unit (ICU) patients depending on mechanical ventilation on day 3 with functional gastrointestinal tract. Patients were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on, for 30 days. Blood samples were collected on days 4 and 15. We determined the GH, C-peptide, 25-OH vitamin-D, and IGF-1. Statistics by ANCOVA., Results: Blood samples of 26 patients were available on day 4, and 23 on day 15. While age and severity of disease did not differ, diabetes was more frequent in the HMB group (p = 0.041), and obesity was more frequent in the placebo group (p = 0.021). Glucose intake, blood glucose (BG) and amount of insulin to maintain blood glucose between 6 and 8 mM did not differ between groups. There was no difference between groups for C-peptide, GH, IGF-1, and 25-OH vitamin-D. IGF-1 increased significantly from day 4-15 (p = 0.026) in both groups., Conclusion: Subject to possible insufficient power of the study, we did not reach conclusive results. HMB intervention does not affect significantly the plasma concentrations of insulin, GH/IGF axis activity, C-peptide, and 25-OH vitamin-D., Gov Identifier: NCT03628365., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The extraction and commercialization of palm hearts is the most profitable activity involving the peach palm (Bactris gasipaes ), while consumption of its fruits is limited to Amazonian communities. The excessive attention paid to the implementation of germplasm banks contributed to the lack of development of high-performance varieties, limiting the production and consumption of peach palm fruits and by-products. In addition, with the fragmentation of the Amazonian rainforest, wild populations are in danger of extinction. The species domestication, initiated by Native Amazonians, generated a large variety of peach palm populations, as evidenced by the diversity in fruit sizes and quality. Some advances in agronomic traits also took place. However, more research needs to be conducted to understand the implications of climatic changes on plant physiological performance. Indeed, the key point is that the exploitation of the full potential of B. gasipaes has not been completely exploited. Therefore, understanding the state-of-the-art research on the peach palm with a focus on its underutilized resources is essential for expanding plantations and, consequently, promoting the market expansion of the peach palm as a fruit crop.

Purpose: The purpose of this study is to determine the incidence of gastric tube abnormalities after SG and its relationship with esophagitis progression., Methods: Retrospective study which included 459 patients in the postoperative period of SG who underwent an esophagogastroduodenoscopy in both pre- and postoperative periods. The main studied variables were presence of gastric tube abnormalities (dilation, neofundus, twist, and hiatal hernia) and esophagitis progression., Results: Among the 459 patients who underwent SG, 393 (85.6%) were women, and 66 (14.4%) men, with mean age of 40.4 years. Mean preoperative BMI was 39.70 kg/m 2 . In total, 20.3% of the sample presented progression of esophagitis after surgery. Among the whole sample, 130 (28.3%) presented with an abnormality of the remnant gastric tube. The most common alteration was gastric dilation, which occurred in 16.1% of the patients, followed by gastric twist (10.7%), neofundus (7.4%), and hiatal hernia (0.2%). Patients who presented with any abnormality of the gastric tube were significantly prone to presenting esophagitis progression (p = 0.013). When analyzing each morphological abnormality isolated, there was no statistically significant correlation., Conclusion: Abnormalities of the gastric tube are not uncommon after SG and seems to contribute partially to the relevant rates of GERD and esophagitis after this surgery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dengue virus (DENV) infection represents a worldwide public health concern and can cause damage to multiple organs, including the kidney. In this work, we investigated the histopathological changes caused by dengue virus infection along with the detection of inflammatory mediators, cytokines, and cell expression patterns in the renal tissue of three fatal cases in children. Hematoxylin and Eosin staining was performed to analyze these histopathological changes. Immunohistochemistry allowed for the detection of immunological inflammatory markers in renal tissues that were quantified and further analyzed. Vascular congestion, edema and glomerular infiltrate were observed in the three cases, in addition to the thickening of the matrix area around the glomerular capillaries and mononuclear infiltrate associated with vascular congestion in the medullary region. The renal tissues exhibited collagen deposition and high expression of CD68 + Mø, CD8 + T, CD56 + cells and MMP-9, and the cytokine profile was mainly characterized by the expression of IFN-γ and TNF-α. Additionally, the expression of RANTES, VEGFR-2 and VCAM-1 were observed. The replication of DENV was evidenced by the detection of the NS3 protein. These results contributed to clarifying the main factors that may be involved in changes in the renal tissue of fatal cases of dengue in children.

Background: The optimal treatment of symptomatic Morton's neuroma remains unclear; conservative methods are sometimes ineffective and neurectomy has significant rates of patient dissatisfaction. The aim of this study was to evaluate the outcome of minimally invasive distal metatarsal metaphyseal osteotomy (DMMO) and percutaneous release of the deep transverse metatarsal ligament (DTML) in patients with Morton's neuroma., Methods: Between January 2018 and November 2019, 27 patients (29 feet) diagnosed with Morton's neuroma after clinical and radiological evaluation underwent DMMO and percutaneous DTML release. The primary clinical outcomes were pain (VAS) and function (AOFAS score). Secondary outcomes included patient satisfaction, complications, and radiographic outcomes. Patients were followed up for a minimum of two years., Results: The median age of the participants was 66 years (range 48-79) and the follow-up time was 28 months (24-47). There was a decrease of 5.7 points in the VAS for pain (p < .001) and an increase of 19.9 in AOFAS (p < .001) after the surgical procedure. There was one case of superficial infection and one patient required resection of the neuroma (neurectomy). The majority of patients (89.7%) were satisfied and considered the procedure outcome as excellent or good., Conclusion: Treatment of Morton's neuroma with minimally invasive distal metatarsal metaphyseal osteotomy and percutaneous release of the deep transverse metatarsal ligament showed significant improvement in pain and function with a low incidence of complications and a high rate of personal satisfaction., (© 2022. The Author(s) under exclusive licence to SICOT aisbl.)

Background: Congenital anomalies are associated with several clinical and epidemiological complications. Following the Zika epidemic onset in Latin America, the incidence of congenital anomalies increased in Brazil. This study aimed to determine the frequency of congenital anomalies in one Brazilian state and assess potential factors associated with them., Methods: This cross-sectional descriptive study was based on data concerning congenital anomalies recorded in the Brazilian Live-Born Information System during the Zika epidemic in Mato Grosso do Sul state from 2015 to 2018. Congenital anomalies were stratified according to year of birth and classified using ICD-10 categories., Results: In total, 1,473 (0.85%) anomalies were registered. Within the number of cases recorded, microcephaly showed the greatest frequency and variations, with a 420% increase observed in the number of cases from 2015 to 2016. We identified an increase in the incidence of central nervous system anomalies, with the highest peak observed in 2016 followed by a subsequent decrease. Musculoskeletal, nervous, and cardiovascular system anomalies, and eye, ear, face, and neck anomalies represented 73.9% of all recorded anomalies. There was an increased chance of congenital anomalies in uneducated (odds ratio [OR] 5.56, 95% confidence interval [CI] 2.61-11.84) and Indigenous (OR 1.32, 95% CI 1.03-1.69) women, as well as among premature births (OR 2.74, 95% CI 2.39-3.13)., Conclusions: We estimated the incidence of congenital anomalies during the Zika epidemic. Our findings could help to support future research and intervention strategies in health facilities to better identify and assist children born with congenital anomalies., (© 2022. The Author(s).)

Objective: To study the profile of the practice of arthroscopy among ankle and foot surgeons in Brazil and its evolution in recent years., Methods: Observational, cross-sectional study, using a survey sent to all members of the Associação Brasileira de Medicina e Cirurgia do Tornozelo e Pé (ABTPé) in 2017 and 2019., Results: In total, 75 surgeons participated in 2017 and 82 in 2019 and most had over 10 years of experience. Of these, 56 participants in 2017 (75%) and 68 in 2019 (82%) used arthroscopy. The number of specialists with no to five years of experience (p = 0.027) and who learned the technique during fellowship (p = 0.007) increased. The use of the 4.0 mm optics and 30° optics (p = 0.040) increased whereas the routine use of traction (p = 0.049) and radiofrequency (p = 0.002) decreased. The main pathology treated with anterior ankle arthroscopy was bone injury. The most frequent complication was neuropraxia., Conclusion: Most of the foot and ankle surgeons who use arthroscopy have more than 10 years of experience, performed anterior access, and are concentrated in the Southeast region of the country. The number of younger surgeons who learned the technique during fellowship increased. Level of Evidence III, Cross-Sectional Comparative Study., Competing Interests: All authors declare no potential conflict of interest related to this article.

Background: There is no specific recommendation for nutrition therapy for critically ill older adults. However, targeting energy and protein balance and avoiding fasting could improve outcomes in this population with high-risk nutrition outcomes. This study aimed to evaluate the associations between nutrition and mortality/functionality in critically ill older patients., Methods: A single-center retrospective observational study of critically ill patients aged 65 years or older was conducted. We extracted data from the dietitian evaluations on energy, protein, and the type of diet (fasting, oral, enteral, or parenteral) prescribed in the first week of intensive care unit admission. Primary outcomes were intrahospital mortality and independence and functional capacity evaluated after hospital discharge., Results: Of the 2043 patients screened, 533 were included in the study. Most patients were men (52.1%), with a median age of 73 (68-78) years. Overall, the intrahospital mortality rate was 53.8%. Simplified Acute Physiology Score 3 (SAPS 3), serum albumin and C-reactive protein levels, and surgical patients were independently associated with fasting in a multivariate analysis. The multivariate regression analyses showed that SAPS 3, serum albumin level, and fasting were independently associated with mortality. Each fasting day increases the risk of mortality by 16.7%. Also, independence and functional capacity were not related to nutrition prescription., Conclusion: Older adults (65 years or older) constitute a fragile population in whom nutrition breaks were associated with increased hospital mortality. Furthermore, a prospective clinical trial is necessary to establish the best strategy to feed this population., (© 2022 American Society for Parenteral and Enteral Nutrition.)

In the Northeast of Brazil, Ceará was the second state most impacted by COVID-19 in number of cases and death rate. Despite that, the early dynamics of the pandemic in Ceará was not yet well understood due the low genomic surveillance of SARS-CoV-2 in 2020. In this study, we analyze the circulating lineages and the genomic variation of the virus in Ceará state. Thirty-four genomes were sequenced and combined with sequences available in GISAID database from March 2020 to June 2021 to compose the study dataset. The most prevalent lineages detected were B.1.1.33, in 2020, and P.1, in 2021. Other lineages were found, such as P.2, sublineages of P.1, B.1, B.1.1, B.1.1.28 and B.1.212. Analyzing the mutations, a total of 202 single-nucleotide polymorphisms (SNPs) were identified among the 34 genomes sequenced, of which 127 were missense, 74 synonymous, and one was a nonsense mutation. Among the missense mutations, C14408T, A23403G, T27299C, G28881A G28883C, and T29148C were the most prevalent within the dataset. Although SARS-CoV-2 sequencing data was limited in 2020, our results could provide insights to better understand the genetic diversity of the circulating lineages in Ceará., 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 © 2022 Elsevier B.V. All rights reserved.)

The genus Orthopoxvirus (OPXV) of the family Poxviridae comprises several viruses that are capable of infecting a wide range of hosts. One of the most widespread OPXVs is the Vaccinia virus (VACV), which circulates in zoonotic cycles in South America, especially in Brazil, infecting domestic and wild animals and humans and causing economic losses as well as impacting public health. Despite this, little is known about the presence and/or exposure of neotropical primates to orthopoxviruses in the country. In this study, we report the results of a search for evidence of OPVX infections in neotropical free-living primates in the state of Minas Gerais, southeast Brazil. The sera or liver tissues of 63 neotropical primates were examined through plaque reduction neutralization tests (PRNT) and real-time PCR. OPXV-specific neutralizing antibodies were detected in two sera (4.5%) from Callithrix penicillata , showing 55% and 85% reduction in plaque counts, evidencing their previous exposure to the virus. Both individuals were collected in urban areas. All real-time PCR assays were negative. This is the first time that evidence of OPXV exposure has been detected in C. penicillata , a species that usually lives at the interface between cities and forests, increasing risks of zoonotic transmissions through spillover/spillback events. In this way, studies on the circulation of OPXV in neotropical free-living primates are necessary, especially now, with the monkeypox virus being detected in new regions of the planet.

Objectives: This retrospective case series study aimed to investigate the demographic and clinical patterns of primary stabbing headache (PSH). In addition, we tried to identify subgroups of treatment responses in a neurology outpatient consultation at a Portuguese tertiary hospital., Methods: Clinical records were retrospectively reviewed and patients meeting the International Classification of Headache Disorders, 3rd edition, criteria for PSH were identified from January 2014 to December 2020. We collected data regarding demographic characteristics, clinical features of the headache, primary headache comorbidities, and information about treatment-related do PSH., Results: Of 1857 patients, 32 (1.7%; mean [SD] age of onset 56 [3.5] years) had the final diagnosis of PSH. Regarding headache characteristics, 20 patients (62.5%) reported episodes of stabbing in fixed locations and 12 (37.5%) in multiple areas; the duration of each attack was between ≤5 s (seven [21.9%]), 5-60 s (20 [62.5%]), and ≥60 s (five [15.6%]). In all, 18 patients (56.3%) had an episodic course (vs. six of 32 [18.8%] an acute course and eight of 32 [25%] a chronic course). In all, 17 patients started medical treatment (53.1%), with total or partial improvement in 10 (58.8%) of them. It was found that patients with pain in fixed locations had a better response to treatment when compared to patients with multiple locations, in a statistically significant way (eight of 11 vs. two of six, p = 0.023)., Conclusion: In our sample, the mean age of onset of PSH was >50 years and there was a wide range of PSH duration. The duration of each attack (>5 s), the pain in fixed locations, non-daily episodes of the pain in each attack, and the intermittent course of headache were the most prevalent clinical features. Finally, patients with stabbing in localized areas had a better response to treatment., (© 2022 American Headache Society.)

Background: The osmotin from the medicinal plant Calotropis procera (CpOsm) has characteristics similar to adiponectin, a human protein with immunoregulatory actions., Purpose: This study aimed to investigate whether recombinant osmotin inclusion bodies from C. procera (IB/rCpOsm) produced in E. coli BL21(DE3) can prevent infection-induced inflammation. A virulent strain of Listeria monocytogenes was used as an infection model., Methods: Cells of E. coli BL21(DE3) carrying the plasmid pET303-CpOsm were used to express the recombinant osmotin, which accumulated at reasonable levels as inclusion bodies (IB/rCpOsm). IB/rCpOsm were purified from induced cells and SDS-polyacrylamide gel electrophoresis followed by mass spectrometry analyses confirmed the identity of the major protein band (23 kDa apparent molecular mass) as CpOsm. Peritoneal macrophages (pMØ) from Swiss mice were cultured with IB/rCpOsm (1 or 10 µg/ml) in 96-well plates and then infected with L. monocytogenes. IB/rCpOsm (0.1, 1 or 10 mg/kg) was also administered intravenously to Swiss mice, which were then infected intraperitoneally with L. monocytogenes., Results: Pretreatment of the pMØ with IB/rCpOsm significantly increased cell viability after infection and reduced the intracellular bacterial load. The infiltration of neutrophils into the peritoneal cavity of mice pretreated with IB/rCpOsm at 10 mg/kg (but not 0.1 and 1 mg/kg) was reduced after infection. In these mice, the bacterial load was high in the peritoneal fluid and the liver, but histological damage was discrete. The treatments with IB/rCpOsm at 10 mg/kg significantly increased the expression of the anti-inflammatory cytokine IL-10., Conclusion: This study shows that recombinant osmotin inclusion bodies from C. procera were bioactive and prompted anti-inflammatory actions at therapeutic dosages in the L. monocytogenes infection model., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Little is known about metabolic and nutrition characteristics of patients with coronavirus disease 2019 (COVID-19) and persistent critical illness. We aimed to compare those characteristics in patients with PCI and COVID-19 and patients without COVID-19 infection (non-CO)-primarily, their energy balance., Methods: This is a prospective observational study including two consecutive cohorts, defined as needing intubation for >10 days. We collected demographic data, severity scores, nutrition variables, length of stay, and mortality., Results: Altogether, 104 patients (52 per group) were included (59 ± 14 years old [mean ± SD], 75% men) between July 2019 and May 2020. SAPSII, Nutrition Risk Screening (NRS) score, proportion of obese patients, duration of intubation (18.2 ± 11.7 days), and mortality rates were similar. Patients with COVID-19 (vs non-CO) had lower SOFA scores (P = 0.013) and more frequently needed prone position (P < 0.0001) and neuromuscular blockade (P < 0.0001): lengths of ICU (P = 0.03) and hospital stays were shorter (P < 0.0001). Prescribed energy targets were below those of the ICU protocol. The energy balance of patients with COVID-19 was significantly more negative after day 10. Enteral nutrition (EN) started earlier (P < 0.0001). During the first 10 days, COVID-19 patients received more lipid (propofol sedation) and less protein. Higher admission C-reactive protein (P = 0.002) decreased faster (P < 0.001). Whereas intestinal function was characterized by constipation in both groups during the first 10 days, diarrhea was less common in patients with COVID-19 thereafter., Conclusion: Compared with non-CO patients, COVID-19 patients were not more obese, had lower SOFA scores, and were fed more rapidly with EN, because of a more normal gastrointestinal function possibly due to fewer non-respiratory organ failures: their energy balances were more negative after the first 10 days. Propofol sedation reduced protein delivery., (© 2022 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: The Parkinson disease (PD) is frequently associated with autonomic dysfunctions. However, data regarding the influence of PD on the autonomic responses to postural changes is limited., Objective: To analyze and compare the autonomic responses, evaluated through linear and non-linear methods of heart rate variability, and cardiorespiratory parameters in two groups: Parkinson disease (PDG) and control (CG), at rest and during the active tilt test., Methods: A total of 48 participants were analyzed (PDG: n  = 25;73.40 ± 7.01 years / CG: n  = 23;70.17 ± 8.20 years). The autonomic modulation and cardiorespiratory parameters were evaluated at rest and during the active tilt test. To assess the autonomic modulation the linear indices, at the time (rMSSD, SDNN) and frequency (LF, HF, LF/HF) domains, and the non-linear indices, obtained through the Poincaré plot (SD1, SD2, SD1/SD2), were calculated. The cardiorespiratory parameters evaluated were heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP), peripheral oxygen saturation (SpO 2 ), and respiratory rate., Results: At rest, the PDG presented significantly lower values of rMSSD, SDNN, LF, HF, SD1, SD2, and DBP, and higher values of SpO 2 . During test, in the PD group, modifications were observed in HR, and SBP, besides a reduced parasympathetic response, and an increased global modulation. The qualitative analysis of the Poincaré plot showed that the PDG has a lower dispersion of the RR intervals during rest and the active tilt test., Conclusion: Individuals with PD present reduced global variability and parasympathetic modulation at rest, and reduced parasympathetic response and damage in HR regulation when performing the active tilt test, compared with controls., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. 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/).)

Significance: A growing body of research supports the significant role of cerebrovascular abnormalities in neurological disorders. As these insights develop, standardized tools for unbiased and high-throughput quantification of cerebrovascular structure are needed. Aim: We provide a detailed protocol for performing immunofluorescent labeling of mouse brain vessels, using thin ( 25    μ m ) or thick (50 to 150    μ m ) tissue sections, followed respectively by two- or three-dimensional (2D or 3D) unbiased quantification of vessel density, branching, and tortuosity using digital image processing algorithms. Approach: Mouse brain sections were immunofluorescently labeled using a highly selective antibody raised against mouse Cluster of Differentiation-31 (CD31), and 2D or 3D microscopy images of the mouse brain vasculature were obtained using optical sectioning. An open-source toolbox, called Pyvane, was developed for analyzing the imaged vascular networks. The toolbox can be used to identify the vasculature, generate the medial axes of blood vessels, represent the vascular network as a graph, and calculate relevant measurements regarding vascular morphology. Results: Using Pyvane, vascular parameters such as endothelial network density, number of branching points, and tortuosity are quantified from 2D and 3D immunofluorescence micrographs. Conclusions: The steps described in this protocol are simple to follow and allow for reproducible and unbiased analysis of mouse brain vascular structure. Such a procedure can be applied to the broader field of vascular biology., (© 2022 The Authors.)

Objectives: The objective of this study is to synthesize the current literature about the relationship between the occurrence of diabetes insipidus (DI), its diagnosis criteria, and management after withdrawal of vasopressin (VP) in critically ill., Data Sources: This scoping review followed the recommendations of Preferred Reporting Items for Systematic Review and Meta-Analyses for Scoping Review (PRISMA-ScR). The search literature was conducted in MEDLINE and EMBASE databases, until March 2022. A manual search was also conducted in order to include articles that were not identified in the initial search performed in the databases., Study Selection and Data Extraction: The selection of studies and extraction of data were carried out in a paired and independent manner. There was no restriction regarding the language of publication of the included manuscripts., Data Synthesis: The analysis included 17 studies (16 case reports and one retrospective cohort). All studies used VP, with a median time of drug infusion of 48 hours (IQR: 16-72) and DI incidence of 1.53%. The diagnosis of DI was based on diuresis output and concomitant hypernatremia or changes in serum sodium concentration, with median time to symptoms onset after discontinuation of VP of 5 hours (IQR: 3-10). The treatment of DI consisted mainly of fluid management and the use of desmopressin., Conclusions: DI after VP withdrawal was present in 51 patients described in 17 studies, but diagnosis and management varied among each report. Using the available data, we propose a diagnosis suggestion and a flowchart for managing patients with DI after withdrawal of VP in the Intensive Care Unit. Multicentric collaborative research is urgently needed to obtain more quality data on this topic., How to Cite This Article: Pérsico RS, Viana MV, Viana LV. Diabetes Insipidus after Vasopressin Withdrawal: A Scoping Review. Indian J Crit Care Med 2022;26(7):846-852., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; Jaypee Brothers Medical Publishers (P) Ltd.)

Jatropha mollissima is endemic to Brazil and is used for traditional medicinal purposes, including the treatment of snakebite. In this study, latex obtained from this plant was fractioned using reversed-phase chromatography, and the fractions were then screened for peptides. A 755 g/mol peptide was obtained, and MS/MS analyses indicated it had a cyclic sequence (Pro-Leu-Gly-Val-Leu-Leu-Tyr). This peptide sequence was present in the Jatropha genome database, and an identity value of 90.71%, an E-value of 0.0, and a score of 883 with NO-associated protein 1/chloroplastic/mitochondria of Jatropha curcas were obtained from the NCBI nonredundant protein sequence (nr) database. Molecular docking analyses performed with the peptide against a metalloendopeptidase belonging to Crotalus adamanteus snake venom suggested the cyclic peptide establishes favorable interactions with the catalytic site of the enzyme. Therefore, it could inhibit enzyme catalysis. This belief was corroborated by the formation of 6 hydrogen bonds with the linear form of the peptide. Tighter complexation of the cyclic form (41 kcal/mol more energetic) revealed better spatial blocking. The linear form outperformed the cyclic form in complexing the required energy, recruiting more catalytic residues (6/2), and in establishing more hydrogen bonds (6/3). However, cyclic folding provided a more significant spatial block within the catalytic site. The set of results suggests that the cycle peptide, here called Jatromollistatin, which was previously described as jatrophidin and pohlianin A in two other species of Jatropha, is a promising candidate to inhibit venom proteases. This belief is corroborated by the topical use of the latex for initial treatment of snakebites., (© 2022 John Wiley & Sons Ltd.)

Background: Intrinsic changes in Parkinson's disease (PD) affect the autonomic nervous system, and the disease course can aggravate the initial condition. Although the impact of time since disease onset on autonomic modulation has already been studied in other populations, this has not yet been investigated in PD., Objective: To investigate the impact of the length of time since diagnosis on the cardiac autonomic modulation of individuals with PD and compare with healthy individuals., Methods: Fifty participants were divided into three groups: a control group (CG; n = 24) and two groups with PD, divided according to the median length of time since diagnosis (median = 5.5 years): below the median (PG1; n = 13) and above the median (PG2; n = 13). To evaluate cardiac autonomic modulation, heart rate was obtained beat-to-beat in the supine position over a 30-min period, and heart rate variability (HRV) indices were calculated using linear methods in the time and frequency domains., Results: There were no significant differences in HRV indices between the PG groups, or between the three groups regarding Mean RR, LFun, HFun and LF/HF ratio. Significant reductions in the RMSSD, SDNN, pNN50, LFms2 and HFms2 indices were observed in PG1 and PG2, compared with CG., Conclusions: The cardiac autonomic modulation of individuals with PD was not influenced by the time since diagnosis. However, reduced parasympathetic and global modulation were observed in these individuals, compared with controls. These results emphasize the importance of aerobic exercise for improving autonomic modulation among individuals with PD.

The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11 th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA 1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI -0.66 to -0.59) and body weight by 0.60 kg (95% CI -0.64 to -0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA 1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Background: Within the pathogenic bacterial species Corynebacterium genus, six species that can produce diphtheria toxin ( C. belfantii , C. diphtheriae, C. pseudotuberculosis , C. rouxii , C. silvaticum and C. ulcerans ) form a clade referred to as the C. diphtheria complex. These species have been found in humans and other animals, causing diphtheria or other diseases. Here we show the results of a genome scale analysis to identify positive selection in protein-coding genes that may have resulted in the adaptations of these species to their ecological niches and suggest drug and vaccine targets., Methods: Forty genomes were sampled to represent species, subspecies or biovars of Corynebacterium . Ten phylogenetic groups were tested for positive selection using the PosiGene pipeline, including species and biovars from the C. diphtheria complex. The detected genes were tested for recombination and had their sequences alignments and homology manually examined. The final genes were investigated for their function and a probable role as vaccine or drug targets., Results: Nineteen genes were detected in the species C. diphtheriae (two), C. pseudotuberculosis (10), C. rouxii (one), and C. ulcerans (six). Those were found to be involved in defense, translation, energy production, and transport and in the metabolism of carbohydrates, amino acids, nucleotides, and coenzymes. Fourteen were identified as essential genes, and six as virulence factors. Thirteen from the 19 genes were identified as potential drug targets and four as potential vaccine candidates. These genes could be important in the prevention and treatment of the diseases caused by these bacteria., Competing Interests: Debmalya Barh and Vasco Azevedo are Academic Editors for PeerJ., (© 2022 Canário Viana et al.)

Background: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients., Methods: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment., Results: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48-68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8-12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference -3.7%, 95% CI -18.8-11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups., Conclusions: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone., Competing Interests: Conflict of interest: L. Sekine has nothing to disclose. Conflict of interest: B. Arns has nothing to disclose. Conflict of interest: B.R. Fabro has nothing to disclose. Conflict of interest: M.M. Cipolatt has nothing to disclose. Conflict of interest: R.R.G. Machado received support from “Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)” (2017/24769-2). Conflict of interest: E.L. Durigon has nothing to disclose. Conflict of interest: E. Parolo has nothing to disclose. Conflict of interest: J.A.S. Pellegrini has nothing to disclose. Conflict of interest: M.V. Viana has nothing to disclose. Conflict of interest: P. Schwarz has nothing to disclose. Conflict of interest: T.C. Lisboa has nothing to disclose. Conflict of interest: J.M.S. Dora has nothing to disclose. Conflict of interest: J.P. Portich has nothing to disclose. A.A. Paz has nothing to disclose. L. Silla has nothing to disclose. A.M. Balsan has nothing to disclose. Conflict of interest: F.d-S. Schirmer has nothing to disclose. Conflict of interest: J.P.M. Franz has nothing to disclose. Conflict of interest: L.M. da-Silveira has nothing to disclose. Conflict of interest: R.C. Breunig has nothing to disclose. Conflict of interest: V. Petersen has nothing to disclose. Conflict of interest: M. Sosnoski has nothing to disclose. Conflict of interest: N.F. Mesquita has nothing to disclose. Conflict of interest: F.C.Z. Volpato has nothing to disclose. Conflict of interest: D. Sganzerla has nothing to disclose. Conflict of interest: M. Falavigna has nothing to disclose. Conflict of interest: R.G. Rosa received research grants from Brazilian Ministry of Health. Conflict of interest: A.P. Zavascki is a research fellow of the National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil (304226/2018-1), and receives a research grant not related to this work from Pfizer (WI242215 2018)., (Copyright ©The authors 2022.)

Introduction: Interprofessional education (IPE) offers relevant theoretical, conceptual and methodological approaches to the development of effective teamwork competencies., Objective: To analyse an interprofessional experience of teaching-service-community integration carried out at a public university in the South of Brazil., Methods: A case study with a qualitative approach was carried out. The study's participants were thirty-eight undergraduate dental students who attended the IPE activity between 2012 and 2019. Data collection was developed in two sequential steps that included the application of an online instrument and semi-structured interviews. The textual material was interpreted by content analysis, considering Kirkpatrick's evaluation levels (reaction, learning and behaviour)., Results: In the reaction level, students highlighted the contents provided by the National Curricular Guidelines regarding public health system and teamwork, as well as the pedagogical teaching proposal by tutoring groups, which stimulated students' autonomy. It was observed that the learning was geared towards the development of collaborative teamwork competencies and cultural competencies. In the behaviour level, students perceived positive changes in their attitudes and behaviours towards patients, focused on needs related to life conditions, realising that dentists may work within a team. The elective/optional nature of the experience allied with the absence of other IPE activities in the curricular grid showed to be challenging., Conclusion: IPE in undergraduate education presented positive results related to the reaction, learning and behaviour of dental students. We recommend the inclusion of interprofessional activities of teaching-service-community integration in Dentistry curricular structure to complement uniprofessional education., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Dengue viral (DENV) infections can lead to acute pancreatitis and associated tissue damage. This study examined the pancreas from two fatal cases of DENV for histopathological changes as well as for the detection of cytokines, and other inflammatory mediators. Tissue sections were prepared for examination by ultrastructural and histopathological techniques. Sections from the pancreas of non-infected individuals were prepared in parallel as a control. The presence of viral replication in macrophages was detected by co-staining for the proteins NS3 and CD68 by immunofluorescence. Immunohistochemistry was used to detect cells that expressed cytokines and inflammatory mediators to characterize the inflammatory response. Edema, acinar necrosis and fibrosis areas associated with a mononuclear infiltrate were found in infected tissues. The major site of virus replication appeared to be macrophages based on their exclusive presentation of the viral protein NS3. Pancreatic tissues from the infected individuals also displayed increased levels of high mobility group box-1, caspase-3, gelatinase B and tumor necrosis factor alpha compared to controls. The presence of virus replicating macrophages in the pancreas was associated with multiple changes in tissue structure that included elevated levels of cytokines and inflammatory markers that may differentiate acute pancreatitis due to DENV infections from other causes., Competing Interests: The authors have declared that no competing interests exist.

Background: Autologous grafting is widely used in orthopaedic surgery because of its high osteogenic capacity, immunologic compatibility, for the absence of risk of disease transmission, and for not requiring a bone bank. The posterior-superior calcaneal tuberosity is an option for obtaining a cortical and cancellous structural bone. This study aims to describe the operative technique and complications observed at the donor site of the posterior-superior calcaneal tuberosity., Methods: Patients who underwent graft harvesting from the posterior-superior calcaneal tuberosity were retrospectively evaluated by pain outcomes, imaging tests, and intra- and postoperative complications., Results: Twenty patients with a median age of 69 years (range 48-77) and follow-up of 16 months (12-26) were assessed. Median postoperative pain at the donor site was 0 (0-6), with 2 patients reporting persistent local pain. No case of Achilles tendon rupture or intra- or postoperative calcaneal fracture were identified. One patient developed a superficial infection that was quickly resolved using oral antibiotic therapy., Conclusion: The posterior-superior calcaneal tuberosity is an alternative source of autologous graft with low donor site morbidity., Level of Evidence: Level IV, case series.