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Milena Barbosa Porto,1 Geovanna da Mata e Castro,1 Samara Socorro Silva Pereira,2 Elza Maria Gonçalves Santos Uchoa,2 Raffael Zatarin,3 Lysa Bernardes Minasi,1 Aparecido D da Cruz1– 3 1Graduate Program in Genetics, School of Medical and Life Sciences, Pontifical Catholic University of Goiás, Goiânia, GO, Brazil; 2Federal University of Goiás, Graduate Program in Genetics and Molecular Biology, Goiânia, GO, Brazil; 3Clinical Genetics Service, Center for Rehabilitation and Readaptation Dr. Henrique Santillo, State Health Secretary of Goiás, Goiânia, GO, BrazilCorrespondence: Aparecido D da Cruz, Email acruz@pucgoias.edu.brAbstract: Baker-Gordon Syndrome (BAGOS) is a genetically determined 4 (NDD), represented by a phenotypic spectrum of moderate to severe intellectual disability, resulting from mutations in the synaptotagmin 1 (SYT1) gene. Its prevalence is estimated at 1:1,000,000 and the known gene variants have indicated complete penetrance with variable expressivity. SYT1 is a membrane trafficking protein in presynaptic vesicles, which exerts a complex influence on synaptic transmission, with fundamental roles in the release of neurotransmitters and facilitators of endocytosis, impacting both neurotransmission and neuron plasticity. The current case report describes the first Brazilian male patient diagnosed at 17-year-old, and the 39th reported case globally using whole-exome sequencing. A de novo heterozygous missense mutation at chr12q:79448958 (NM_005639.2; c.1103T>C; p.Ile368Thr) in the SYT1 was found and classified as a pathogenic variant. The proband’s clinical phenotype was compatible with BAGOS, involving behavioral changes such as irritability and severe intellectual disability. Knowledge about the mechanism of action and the extent of the genotypic and phenotypic presentations of the mutations in the SYT1 is still unfolding. Thus, we aimed to describe additional genotype–phenotype correlation for BAGOS, contributing to the expansion of the existing knowledge of such a heterogeneous ultra-rare syndrome, and, therefore, improve its diagnostic yield, case management, and therapeutic journey for future patients. Keywords: SYT1, hypotonia, congenital malformations, NDD, WES

AIM OF THE STUDY: Zanthoxylum rhoifolium Lam. (Rutaceae) is locally known as 'mamica de cadela', and its bark is popularly used for toothache and earache. The objective of this study was to investigate the antinociceptive effect of the ethanolic extract from this species' stem bark (EtOH), its fractions of partition (hexane-HEX, ethyl acetate-AcOEt, aqueous-AQ) and lupeol (a triterpene obtained from HEX) in models of acute pain. MATERIALS AND METHODS: Male and female Swiss mice (25-35 g, n=6-12 animals/group) were used to assess acute toxicity and nociception (Animal Ethics Committee/UFPI, No. 09/2008). Acute toxicity was studied up to 2 g/kg p.o. of EtOH. In the formalin test (2%, 20 microL/paw), the licking time of the stimulated paw was quantified during the first 5 min (first phase) and at 15-30 min (second phase), 1h after oral treatment with EtOH, HEX, AcOEt or saline, and 30 min after use of morphine-MOR (5 mg/kg i.p.). The same response evoked by capsaicin (2 microg/20 microL/paw) was quantified during 5 min, after administration of EtOH, HEX, AcOEt, AQ, saline and MOR. The licking time of the paw that was stimulated with glutamate (10 micromol/20 microL) was measured (15 min) after treatment with EtOH, HEX, AcOEt, AQ, lupeol, saline or MK801 (0.03 mg/kg, i.p.). Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of EtOH (250 mg/kg p.o.) and HEX (500 mg/kg p.o.). RESULTS: The animals did not exhibit any acute toxicity to EtOH (up to 2 g/kg p.o.), so it was not possible to calculate the LD50. EtOH, HEX and AcOEt (62.5-250 mg/kg) produced a significant antinociceptive effect in the formalin and capsaicin tests. However, AQ was ineffective. EtOH, HEX, AcOEt and lupeol reduced the glutamate-evoked nociceptive response, but AQ had no effect. EtOH and HEX did not alter the locomotion of animals in the open-field or rota-rod tests, which suggest a lack of a central depressant effect. CONCLUSION: The results confirm the popular use of Zanthoxylum rhoifolium as an analgesic, and contribute to the pharmacological knowledge of this species because it was shown that EtOH and its less polar partition fractions (HEX, AcOEt) have an antinociceptive effect in models of chemical nociception, and that lupeol appears to be one of the constituents responsible for this effect. [ABSTRACT FROM AUTHOR]

Complete transposition of the great arteries (TGA) is the most common cause of cyanosis in the first week of life. Prenatal diagnosis helps with counseling, planning delivery, and postnatal management for resource-rich health services. In a resource-limited setting, postnatal diagnosis is the norm. This work examines cases of complete TGA in one center in Cambodia without prenatal testing. Twenty-four cases were studied over 5 years. Complex TGA was frequently seen. The majority had normal coronary anatomy and arterial switch operation (ASO) was performed in most cases with a favorable outcome., (© 2024 Wiley Periodicals LLC.)

Objectives: Clinical parameters along with echocardiographic markers are used to interrogate the haemodynamics in persistent pulmonary hypertension of the newborn (PPHN). The aim of this study was to compare different echocardiographic markers in recent cohort of newborn infants with and without PPHN., Methods: In this retrospective study, common echocardiographic markers were examined in infants>34 weeks' gestation with PPHN (cases) and without PPHN (controls). Infants with congenital heart disease were excluded. Binary regression testing was used to evaluate echocardiographic markers predicting PPHN and death. In addition, diagnostic accuracy testing of echocardiographic markers using ROC was also performed. Intra-observer reliability for echocardiographic markers was examined using coefficient of variation (CoV) and intraclass correlation., Results: Fifty-two infants were studied; 22 (42 %) infants with PPHN had significantly higher oxygen requirement, oxygenation index and ventilation days when compared with controls. Echocardiographic markers such as TR Vmax, S/D TR, PAAT, TAPSE and eccentricity index (EI) were significantly different between cases and controls. Receiver operator characteristics analysis of echocardiographic markers revealed TR Vmax 0.96 (0.9-1.0), S/D TR 0.95 (0.87-1.0) and end systolic EI 0.94 (0.87-1.0). These markers were found to predict death in this cohort of infants. CoV and Intra-observer reliability was good for various echocardiographic markers., Conclusions: Among the various echocardiographic markers studied, TR Vmax when present along with S/D TR and end systolic EI had good intra-observer reliability and were diagnostic of PPHN and predicted death in this cohort. Future trials could use these markers in studies examining PPHN., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented., Case Report: A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient's past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (<209), and 68 Ga-SSTR PET/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative 68 Ga-SSTR PET/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis., Discussion and Conclusion: This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cidade-Rodrigues, Santos, Calheiros, Santos, Matos, Moreira, Inácio, Souteiro, Oliveira, Jácome, Pereira, Henrique, Torres and Monteiro.)

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women at childbearing age. Anti-Müllerian hormone (AMH) is a widely accepted sensitive marker of ovarian reserve, which has been suggested that could also act as biomarker of ovarian morphology for PCOS diagnosis. Oxidative stress (OS) is known to be associated and have a negative impact factor in several reproductive conditions, including PCOS. However, the relationship between circulating AMH and OS within the follicular fluid (FF), and its potential impact on in vitro fertilization (IVF) outcomes of women with PCOS, remains largely unexplored. A total of 84 women, with PCOS (n = 30) or ovulatory controls (n = 54), were enrolled in this study. Women underwent individualized controlled ovarian stimulation for oocyte retrieval. Blood and FF obtained from mature follicles were collected at the time of oocyte retrieval, for measuring total testosterone, ∆4-androstenedione, progesterone, sex hormone binding globulin (SHBG) and AMH. OS in the FF was assessed by measuring total antioxidant capacity (TAC) through the ferric reducing antioxidant power (FRAP) and lipid peroxidation (LPO) by quantification of malondialdehyde (MDA) levels. Our results demonstrated that women with PCOS had significantly higher plasma levels of AMH, ∆4-androstenedione, total testosterone and a free androgen index (FAI) than observed in non-PCOS controls. In women with PCOS, total testosterone and AMH levels in the FF were also higher, while TAC was lower compared to non-PCOS. Furthermore, circulating AMH levels were positively correlated with ∆4-androstenedione, albeit negatively correlated with TAC. In this study we demonstrated that the susceptibility to OS, as assessed by the total antioxidant capacity in the FF, is higher in women with PCOS and inversely related to AMH levels. This study results lead us to forge the reasonable hypothesis that the greater susceptibility to OS within the follicle microenvironment is potentially at the end of a roadway that starts with elevated ∆4-androstenedione and AMH within the FF, which in turn are mirrored by circulating AMH and androgen levels. Thus, suggesting that circulating AMH levels could act as a surrogate biomarker of follicular fluid oxidative stress in women with PCOS., 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 © 2024 Vale-Fernandes, Moreira, Rodrigues, Pereira, Leal, Barreiro, Tomé and Monteiro.)

Introduction: Metabolic bariatric surgery (MBS) is known to improve the obstetric outcomes of women with obesity and to prevent gestational diabetes (GD). To what extent does MBS decreases GD, without incurring at additional risks is a matter of concern., Methods: A retrospective case-control study to compare the pregnancy outcomes of women previously submitted to MBS to those of age and preconception body mass index (PC BMI) matched non-operated controls., Results: Pregnancies of women after MBS (n = 79) and matched controls (n = 79) were included. GD was significantly less frequent after MBS (7.6% vs. 19%; p = 0.03). Fasting blood glucose (76.90 ± 0.77 vs 80.37 ± 1.15 mg/dl, p < 0.05; 70.08 ± 1.34 vs. 76.35 ± 0.95 mg/dl; p < 0.05, first and second trimesters respectively) and birth weight (2953.67 ± 489.51 g vs. 3229.11 ± 476.21 g; p < 0.01) were significantly lower after MBS when compared to controls. The occurrence of small-for-gestational-age (SGA) was more frequent after MBS (22.8% vs. 6.3%; p < 0.01), but no longer significant after controlling for smoking habits (15.5% vs. 6%, p = 0.14). There were no significant differences in gestational weight gain, prematurity rate nor mode of delivery between groups., Conclusion: MBS was associated with a lower prevalence of GD than observed in non-operated women with the same age and BMI. After controlling for smoking, this occurred at the expense of a lower birth weight. Our data reinforces the hypothesis that MBS has body weight independent effects on glucose kinetics during pregnancy with distinctive impacts for mother and offspring, which need to be balanced., (© 2024. The Author(s).)

Single-domain antibodies (sdAbs) hold promise for developing new biopharmaceuticals to treat neglected tropical diseases (NTDs), including snakebites, which are severe and occur frequently. In addition, limitations of conventional snakebite treatments, especially in terms of local action, and the global antivenom crisis incentivize the use of this biotechnological tool to design next-generation snakebite antivenoms. Conventional antivenoms for snakebite treatment are usually composed of immunoglobulin G or F(ab') 2 fragments derived from the plasma of immunized animals. sdAbs, the smallest antigen-binding fragments, are derived from the variable domains of camelid heavy-chain antibodies. sdAbs may have some advantages over conventional antivenoms for local toxicity, such as better penetration into tissues due to their small size, and high solubility and affinity for venom antigens due to their unique antigen-binding loops and ability to access cryptic epitopes. We present an overview of current antivenom therapy in the context of sdAb development for toxin neutralization. Furthermore, strategies are presented for identifying snake venom's major toxins as well as for developing antisnake toxin sdAbs by employing proteomic tools for toxin neutralization., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to examine the variation between clinician-recorded and continuously downloaded invasive blood pressure (BP)., Study Design: Prospective study where invasive BP data were downloaded every 10 seconds for the first week of life. Hourly clinician-recorded BP was recorded. Agreement between the two methods were examined., Results: A total of 1,180 BP measurements were examined from 42 preterm infants with a mean (standard deviation [SD]) gestation and birthweight of 25.7 weeks (1.4) and 802 g (177) respectively. The mean (SD) bias was -0.11 mm Hg (3.17), but the 95% limits of agreement (LOA) varied between -6.3 and +6.1 mm Hg. Inotrope usage was significantly higher for BP measurements that fell in the 5% outliers when compared with those that fell within the 95% LOA (62.7 vs. 44.6%, p  = 0.006)., Conclusion: Clinicians showed no systematic bias to over- or underrecord BP, but some of the greatest differences were found in infants receiving inotropes., Key Points: · BP is a commonly recorded cardiovascular parameter in the neonatal intensive care unit.. · Invasively measured BP remains the gold standard.. · Clinician-recorded BP showed no systematic bias in over-or underrecording invasive BP.., Competing Interests: None declared., (Thieme. All rights reserved.)

Plasmodium falciparum is known to cause severe malaria, current treatment consists in artemisinin-based combination therapy, but resistance can lead to treatment failure. Knowledge concerning P. falciparum essential proteins can be used for searching new antimalarials, among these a potential candidate is shikimate dehydrogenase (SDH), an enzyme part of the shikimate pathway which is responsible for producing endogenous aromatic amino acids. SDH from P. falciparum (PfSDH) is unexplored by the scientific community, therefore, this study aims to establish the first protocol for active PfSDH expression. Putative PfSDH nucleotide sequence was used to construct an optimized expression vector pET28a+PfSDH inserted in E. coli BL21(DE3). As a result, optimal expression conditions were acquired by varying IPTG and temperature through time. Western Blot analysis was applied to verify appropriate PfSDH expression, solubilization and purification started with lysis followed by two-steps IMAC purification. Enzyme activity was measured spectrophotometrically by NADPH oxidation, optimal PfSDH expression occur at 0.1 mM IPTG for 48 hours growing at 37 °C and shaking at 200 rpm, recombinant PfSDH obtained after purification was soluble, pure and its physiological catalysis was confirmed. Thus, this study describes the first protocol for heterologous expression of PfSDH in soluble and active form.

Introduction: Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be split into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and post-prandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or SG as the first step of SADI-S., Methods: Subjects submitted to SADI-S (n = 7) or SG (n = 7) at a tertiary referral public academic hospital underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively., Results: Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate, and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up., Conclusions: The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. These data provide support for surgeons' choice of a two-step SADI-S without jeopardizing the weight loss outcomes., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Malnutrition is usual in patients referred for endoscopic gastrostomy (PEG). Refeeding syndrome is rarely observed in PEG-fed patients, which could possibly be associated with reduced absorption induced by prolonged starvation. Objective: In patients submitted to PEG after a significant period of fasting, the present study aims to: 1. evaluate the histological/ultrastructural initial changes in the intestinal mucosa, potentially associated with reduced absorption, and 2. assess if these changes could reverse with enteral refeeding. Methods: The present study is an observational, prospective, controlled study. Adult patients with ingestion below 50% of daily needs for at least one month and/or diagnosis of malnutrition were enrolled. Duodenal biopsies were taken at baseline and after 3-6 months of PEG feeding, which then underwent histological/ultrastructural analysis. Random healthy individuals were used as controls. Results: A total of 30 patients (16 men/14 women) aged 67.1 ± 13.5 years were included. Malnutrition was found in 40% of patients. Approximately 14 patients completed follow-up during both periods (46.7%). At baseline: duodenal mucosal atrophy was evident in three patients (10%); the median villi length (MVL) was 0.4 mm (0.25-0.6 mm), with it being shorter than the controls, which was 0.6 mm (0.4-0.7 mm) ( p = 0.006); ultrastructural changes included focal shortening, bending, and disruption of enterocyte microvilli, the presence of citoplasmatic autophagic vacuoles, dilation and vesiculation of the smooth endoplasmic reticulum, and the presence of dilated intercellular spaces with basement membrane detachment. After refeeding, most patients displayed normal histology (92.9%) and increase MVL ( p < 0.001), ultrastructural changes disappeared, and enterocytes resumed a normal appearance, although retaining scarce, small, dense bodies in apical regions from the evolution of previous autophagy. Conclusions: Prolonged fasting induces histological and ultrastructural changes in the intestinal mucosa that may reflect impaired absorption in the early post-PEG period. These changes were reverted after refeeding with enteral nutrition.

Neurotensin (NT) is a gastro-intestinal hormone involved in several pathways that regulate energy and glucose homeostasis. NT was hypothesized to act in synergy with incretin hormones to potentiate its anti-diabetic effects. Additionally, circulating NT levels were shown to rise after bariatric surgery-induced weight loss. Knowledge of NT-secreting cells distribution along the small intestine and its variation according to diabetes status could provide insights on NT role in mediating type 2 diabetes (T2D) improvement after bariatric surgery. So, our aims were to characterize NT-expressing cell distribution along the human small intestine and to compare the relative density of NT-expressing cells in the small intestine of individuals with and without T2D undergoing bariatric surgery for obesity treatment. Autopsy-derived small intestine fragments (n = 30) were obtained at every 20 cm along the entire intestinal length. Additionally, jejunum biopsies (n = 29) were obtained during elective gastric bypass interventions from patients with (n = 10) or without T2D (n = 18). NT-expressing cells were identified by immunohistochemistry and quantified via computerized morphometric analysis. NT-expressing cell density increased along the human small intestine. NT-expressing cell density was significantly higher from 200 cm distal to the duodenojejunal flexure onward, as well as in subjects with T2D when compared to those without T2D. NT-expressing cell density increases along the human small gut, and a higher density is found in individuals with T2D. This finding suggests a potential role for NT in the mechanisms of disease and T2D improvement observed after bariatric surgery., (© 2023. The Author(s).)

Purpose: Weight loss achieved through bariatric metabolic surgery was demonstrated to be effective at reversing chronic kidney dysfunction associated with obesity-related glomerulopathy. However, robust data on how pre-operative kidney status impacts on bariatric metabolic surgery weight loss outcomes is still lacking. The aim of this study was to evaluate the impact of kidney dysfunction on weight loss outcomes after bariatric metabolic surgery., Methods: Patients with obesity to be submitted to gastric bypass surgery underwent a pre-operative evaluation of creatinine clearance, estimated glomerular filtration rate (eGFR), proteinuria, and albuminuria in 24-hour urine. Body mass index (BMI), % total weight loss (%TWL), and % excess BMI loss (%EBMIL) were assessed at 6 and 12 months after surgery., Results: Before surgery, patients (N=127) had a mean BMI of 39.6 ± 3.0 kg/m 2 , and 56.7% (n=72) had a creatinine clearance > 130 mL/min, 23.6% (n= 30) presented proteinuria > 150 mg/24h, and 15.0% (n= 19) presented albuminuria > 30 mg/24h. After surgery, the mean BMI was 27.7 kg/m 2 and 25.0 kg/m 2 at 6 and 12 months, respectively (p<0.0001). The %TWL was lower in patients with pre-operative eGFR < percentile 25 (34.4 ± 5.8% vs 39.4 ± 4.9%, p=0.0007, at 12 months). There were no significant correlations between weight loss metrics and pre-operative creatinine clearance rate, proteinuria, or albuminuria., Conclusion: Early-stage chronic kidney disease (G2) has a negative impact on short-term weight loss outcomes after bariatric metabolic surgery, albeit in a magnitude inferior to the clinically relevant threshold., (© 2023. The Author(s).)

Obesity is a complex, multifactorial and chronic disease. Bariatric surgery is a safe and effective treatment intervention for obesity and obesity-related diseases. However, weight loss after surgery can be highly heterogeneous and is not entirely predictable, particularly in the long-term after intervention. In this review, we present and discuss the available data on patient-related and procedure-related factors that were previously appointed as putative predictors of bariatric surgery outcomes. In addition, we present a critical appraisal of the available evidence on which factors could be taken into account when recommending and deciding which bariatric procedure to perform. Several patient-related features were identified as having a potential impact on weight loss after bariatric surgery, including age, gender, anthropometrics, obesity co-morbidities, eating behavior, genetic background, circulating biomarkers (microRNAs, metabolites and hormones), psychological and socioeconomic factors. However, none of these factors are sufficiently robust to be used as predictive factors. Overall, there is no doubt that before we long for precision medicine, there is the unmet need for a better understanding of the socio-biological drivers of weight gain, weight loss failure and weight-regain after bariatric interventions. Machine learning models targeting preoperative factors and effectiveness measurements of specific bariatric surgery interventions, would enable a more precise identification of the causal links between determinants of weight gain and weight loss. Artificial intelligence algorithms to be used in clinical practice to predict the response to bariatric surgery interventions could then be created, which would ultimately allow to move forward into precision medicine in bariatric surgery prescription., (© 2023. The Author(s).)

Dengue is an infectious disease of global health concern that continues to require surveillance. Serological testing has been used to investigate dengue-infected patients, but specificity is affected by the co-circulation of ZIKA virus (ZIKV), which shares extensive antigen similarities. The goal of this study was the development of a specific dengue virus (DENV) IgG ELISA based on a multi-epitope NS1-based antigen for antibody detection. The multi-epitope protein (T-ΔNS1), derived from a fragment of the NS1-protein of the four DENV serotypes, was expressed in Escherichia coli and purified via affinity chromatography. The antigenicity and specificity were evaluated with sera of mice infected with DENV-1-4 or ZIKV or after immunization with the recombinant ΔNS1 proteins. The performance of the T-ΔNS1-based IgG ELISA was also determined with human serum samples. The results demonstrate that the DENV T-ΔNS1 was specifically recognized by the serum IgG of dengue-infected mice or humans but showed no or reduced reactivity with ZIKV-infected subjects. Based on the available set of clinical samples, the ELISA based on the DENV T-ΔNS1 achieved 77.42% sensitivity and 88.57% specificity. The results indicate that the T-ΔNS1 antigen is a promising candidate for the development of specific serological analysis.

Aim: To evaluate the accuracy of DiaBetter, DiaRem, Ad-DiaRem and 5y-Ad-DiaRem scores' at predicting T2D remission 10 or more years after surgery., Methods: Patients with obesity and T2D (n = 126) submitted to RYGB with 10 or more years of follow-up. It was a unicentric trial. Pre-operative anthropometric and clinical data was retrieved to calculate DiaRem, DiaBetter, Ad-DiaRem and 5y-Ad-DiaRem scores, while a hospital visit was conducted to assess current diabetes status. The area under the receiver operating characteristic (AUROC) curve was calculated as estimate of the scores' accuracy to predict long-term T2D remission., Results: Among the entire cohort (n = 126), 70 subjects (55.6%) achieved and maintained T2D remission 10 or more years after RYGB. The 5y-Ad-DiaRem score was the one that depicted the highest discriminative power (AUROC = 0.838) to predict long-term T2D remission when compared to DiaBetter (AUROC = 0.735), DiaRem (AUROC = 0.721) and Ad-DiaRem (AUROC = 0.720)., Conclusion: The score with highest accuracy to predict long-term T2D remission after RYGB surgery was the 5y-Ad-DiaRem. Yet, the available scores accuracy to predict T2D remission in the long term is still suboptimal, highlighting the unmet need for a better scoring system., (© 2023. The Author(s).)

Tumors present dysfunctional vasculature that limits blood perfusion and hinders immune cells delivery. We aimed to investigate if regular voluntary running promotes tumor vascular remodelling, improves intratumoral immune cells infiltration and inhibits tumor growth. Tumors were induced in C57BL/6 male mice (n=28) by subcutaneous inoculation in the dorsal region with a suspension of RM1 cells (1.5×10 5 cells/500 µL PBS) and randomly allocated into two groups: sedentary (n=14) and voluntarily exercised on a wheel (n=14). Seven mice from each group were sacrificed 14 and 28 days after cells' inoculation to evaluate tumor weight, microvessel density, vessels' lumen regularity and the intratumoral quantity of NKG2D receptors, CD4 + and CD8 + T cells, by immunohistochemistry. The statistical inference was done through a two-way ANOVA. Exercised mice developed smaller tumors at 14 (0.17±0.1 g vs. 0.48±0.2 g, p<0.05) and 28 (0.92±0.7 g vs. 2.09±1.3 g, p<0.05) days, with higher microvessel density (21.20±3.2 vs. 15.86±4.0 vessels/field, p<0.05), more regular vessels' lumen (1.06±0.2 vs. 1.43±0.2, p<0.05), and higher CD8 + T cells (464.95±48.0 vs. 364.70±49.4 cells/mm 2 , p<0.01), after 28 days. NKG2D expression was higher in exercised mice at 14 (263.27±25.8 cells/mm 2 , p<0.05) and 28 (295.06±56.2 cells/mm 2 , p<0.001) days. Regular voluntary running modulates tumor vasculature, increases immune cells infiltration and attenuates tumor growth, in mice., Competing Interests: The authors declare, beyond the absence of any conflict of interest, that the manuscript was built based on the IJSM ethical standards 89., (Thieme. All rights reserved.)

Animal venoms and their chemical compounds have aroused both empirical and scientific attention for ages. However, there has been a significant increase in scientific investigations in recent decades, allowing the production of various formulations that are helping in the development of many important tools for biotechnological, diagnostic, or therapeutic use, both in human and animal health, as well as in plants. Venoms are composed of biomolecules and inorganic compounds that may have physiological and pharmacological activities that are not related to their principal actions (prey immobilization, digestion, and defense). Snake venom toxins, mainly enzymatic and non-enzymatic proteins, and peptides have been identified as potential prototypes for new drugs and/or models for the development of pharmacologically active structural domains for the treatment of cancer, cardiovascular diseases, neurodegenerative and autoimmune diseases, pain, and infectious-parasitic diseases. This minireview aims to provide an overview of the biotechnological potential of animal venoms, with a focus on snakes, and to introduce the reader to the fascinating world of Applied Toxinology, where animal biodiversity can be used to develop therapeutic and diagnostic applications for humans., 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. Published by Elsevier B.V.)

Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients' (n = 192) average body mass index was 41.7 ± 5.4 kg/m 2 . Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered.

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway.

The C-terminal portion of the E protein, known as stem, is conserved among flaviviruses and is an important target to peptide-based antiviral strategies. Since the dengue (DENV) and Zika (ZIKV) viruses share sequences in the stem region, in this study we evaluated the cross-inhibition of ZIKV by the stem-based DV2 peptide (419-447), which was previously described to inhibit all DENV serotypes. Thus, the anti-ZIKV effects induced by treatments with the DV2 peptide were tested in both in vitro and in vivo conditions. Molecular modeling approaches have demonstrated that the DV2 peptide interacts with amino acid residues exposed on the surface of pre- and postfusion forms of the ZIKA envelope (E) protein. The peptide did not have any significant cytotoxic effects on eukaryotic cells but efficiently inhibited ZIKV infectivity in cultivated Vero cells. In addition, the DV2 peptide reduced morbidity and mortality in mice subjected to lethal challenges with a ZIKV strain isolated in Brazil. Taken together, the present results support the therapeutic potential of the DV2 peptide against ZIKV infections and open perspectives for the development and clinical testing of anti-flavivirus treatments based on synthetic stem-based peptides.

Introduction: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial ( Eschericha coli ) or insect cells ( Drosophila melanogaster ). The ZIKV-envelope glycoprotein (E ZIKV ) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The E ZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes., Methods: In this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV., Results: Testing of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses., Conclusion: In conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems., 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 Lunardelli, Almeida, Apostolico, Rezende, Yamamoto, Pereira, Bueno, Pereira, Carvalho, Slhessarenko, de Souza Ferreira, Boscardin and Rosa.)

Gut microbiota imbalance is associated with the occurrence of metabolic diseases such as obesity. Thus, its modulation is a promising strategy to restore gut microbiota and improve intestinal health in the obese. This paper examines the role of probiotics, antimicrobials, and diet in modulating gut microbiota and improving intestinal health. Accordingly, obesity was induced in C57BL/6J mice, after which they were redistributed and fed with an obesogenic diet (intervention A) or standard AIN-93 diet (intervention B). Concomitantly, all the groups underwent a treatment phase with Lactobacillus gasseri LG-G12, ceftriaxone, or ceftriaxone followed by L. gasseri LG-G12. At the end of the experimental period, the following analysis was conducted: metataxonomic analysis, functional profiling of gut microbiota, intestinal permeability, and caecal concentration of short-chain fatty acids. High-fat diet impaired bacterial diversity/richness, which was counteracted in association with L. gasseri LG-G12 and the AIN-93 diet. Additionally, SCFA-producing bacteria were negatively correlated with high intestinal permeability parameters, which was further confirmed via functional profile prediction of the gut microbiota. A novel perspective on anti-obesity probiotics is presented by these findings based on the improvement of intestinal health irrespective of undergoing antimicrobial therapy or not.

The main coronavirus disease 2019 (COVID-19) vaccine formulations used today are mainly based on the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein as an antigen. However, new virus variants capable of escaping neutralization activity of serum antibodies elicited in vaccinated individuals have emerged. The Omicron (B.1.1.529) variant caused epidemics in regions of the world in which most of the population has been vaccinated. In this study, we aimed to understand what determines individual's susceptibility to Omicron in a scenario of extensive vaccination. For that purpose, we collected nasopharynx swab (n = 286) and blood samples (n = 239) from flu-like symptomatic patients, as well as their vaccination history against COVID-19. We computed the data regarding vaccine history, COVID-19 diagnosis, COVID-19 serology, and viral genome sequencing to evaluate their impact on the number of infections. As main results, we showed that vaccination in general did not reduce the number of individuals infected by Omicron, even with an increased immune response found among vaccinated, noninfected individuals. Nonetheless, we found that individuals who received the third vaccine dose showed significantly reduced susceptibility to Omicron infections. A relevant evidence that support this finding was the higher virus neutralization capacity of serum samples of most patients who received the third vaccine dose. In summary, this study shows that boosting immune responses after a third vaccine dose reduces susceptibility to COVID-19 caused by the Omicron variant. Results presented in this study are useful for future formulations of COVID-19 vaccination policies., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study’s purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 ± 0.58 kg/m2) or class 3 (n = 8; BMI 47.79 ± 1.52 kg/m2) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment.

Background: Patent ductus arteriosus (PDA) diameter is a frequently measured echocardiographic parameter when assessing the PDA. Though, there are recommendations to use 2D echocardiography to measure the PDA diameter, there is paucity of data on how PDA diameter compares when measured using 2D and color echocardiography. The aim of this work was to examine the bias and limits of agreement between measuring PDA diameter using color and 2D echocardiography in newborn infants., Methods: This retrospective study examined the PDA using the high parasternal ductal view. Using colour compare, three consecutive cardiac cycles were used to measure PDA diameter at the narrowest point where the PDA joined the left pulmonary artery in both 2D and colour echocardiography by a single operator., Results: The bias between PDA diameter using color and 2D echocardiography was examined in 23 infants (mean gestation: 28.7weeks). The mean (SD, 95% LoA) bias between color and 2D were 0.45(0.23, -0.005 to 0.91) mm., Conclusion: Color measurements exaggerated PDA diameter measurements when compared to 2D echocardiography.

Metabolic syndrome (MS) is recognized as a risk factor for colon cancer (CC). However, how does the interplay between metabolic dysfunction caused by MS and its individual components affect CC microenvironment and prognosis remains unexplored. Angiogenesis and lymphangiogenesis are fundamental processes for tumor progression and dissemination, ensuring oxygen and nutrient delivery and supporting one of the most important pathways of tumor dissemination, contributing to metastasis. Thus, our aim was to evaluate whether the expression of molecular biomarkers involved in angiogenic and lymphangiogenic processes influenced CC clinicopathological features and prognosis in patients with MS. Clinical and pathological data of 300 patients submitted to CC surgical resection at a single tertiary hospital were retrospectively retrieved from hospital records. Tumor tissue microarrays of archived paraffin-embedded blocks were used to assess CD31, VEGF-A and D2-40 tissue expression by immunohistochemistry. The percentage of stained area was quantified by computerized morphometric analysis. No association between tissue expression of angiogenesis and lymphangiogenesis biomarkers and tumor clinical and pathological characteristics was found. However, in subgroup analysis of patients with MS, dysglycemia was associated with lower D2-40 expression (p = 0.007) and high waist-circumference was associated with higher D2-40 (p = 0.0029) and VEGF-A expression (p = 0.026). In an adjusted Cox proportional hazard model CD31 expression was significantly associated with greater disease-free survival (HR=0.62; 95% CI: 0.41-0.95, p = 0.028). No association was found between D2-40 and VEGF-A expression and CC prognosis. Our data reinforces previous reports that suggest the potential use of CD31 as a CC prognostic biomarker. Additionally, our data further supports the evidence for an interplay between metabolic dysfunction, tumor microenvironment, and vascularization pathways., Competing Interests: Competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

We studied changes in the expression of growth-associated protein 43 (GAP43), glial fibrillary acidic protein (GFAP), and calcium-binding proteins (calbindin [Cb] and parvalbumin [Pv]) in the dorsal lateral geniculate nucleus (dLGN) of four capuchin monkeys with laser-induced retinal lesions. The lesions were generated with the aid of a neodymium-YAG dual-frequency laser with shots of different intensity and at different survival time in each animal. The expression of these proteins in the layers of the dLGN was evaluated by performing histodensitometry of coronal sections throughout the nucleus. High-power laser shots administered at the border of the optic disc (OD)-injured fibers resulted in large scotomas. These lesions produced a devastating effect on fibers in this passage, resulting in large deafferentation of the dLGN. The time course of plasticity expressed in this nucleus varied with the degree of the retinal lesion. Topographically, corresponding portions of the dLGN were inferred by the extent of the ocular dominance column revealed by cytochrome oxidase histochemistry in flattened preparations of V1. In the region representing the retinal lesion, the expression of GFAP, GAP43, Pv, and Cb increased and decreased in the corresponding dLGN layers shortly after lesion induction and returned to their original values with different time courses. Synaptogenesis (indicated by GAP43 expression) appeared to be increased in all layers, while "cleansing" of the glial-damaged region (indicated by GFAP expression) was markedly greater in the parvocellular layers, followed by the magnocellular layers. Schematic drawings of optic discs laser lesions and of series of coronal sections of the dLGN, in three monkeys, depicting the areas of the nucleus deafferented by the lesions., (© 2022 Wiley Periodicals LLC.)

Adrenal masses are one of the most common tumors in humans. The majority are benign and non-functioning and therefore do not require immediate treatment. In contrast, the rare adrenal malignant tumors are often highly aggressive and with poor prognosis. Besides usually being detected in advanced stages, often already with metastases, one of the reasons of the unfavorable outcome of the patients with adrenal cancer is the absence of effective treatments. Autophagy is one of the intracellular pathways targeted by several classes of chemotherapeutics. Mitotane, the most commonly used drug for the treatment of adrenocortical carcinoma, was recently shown to also modulate autophagy. Autophagy is a continuous programmed cellular process which culminates with the degradation of cellular organelles and proteins. However, being a dynamic mechanism, understanding the autophagic flux can be highly complex. The role of autophagy in cancer has been described paradoxically: initially described as a tumor pro-survival mechanism, different studies have been showing that it may result in other outcomes, namely in tumor cell death. In adrenal tumors, this dual role of autophagy has also been addressed in recent years. Studies reported both induction and inhibition of autophagy as a treatment strategy of adrenal malignancies. Importantly, most of these studies were performed using cell lines. Consequently clinical studies are still required. In this review, we describe what is known about the role of autophagy modulation in treatment of adrenal tumors. We will also highlight the aspects that need further evaluation to understand the paradoxical role of autophagy in adrenal tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sousa, Pereira and Pignatelli.)

In order to address the global antivenom crisis, novel antivenoms need to present high therapeutic efficacy, broad neutralization ability against systemic and local damage, sufficient safety, and cost-effectiveness. Due to biological characteristics of camelid single-domain antibodies (VHH) such as high affinity, their ability to penetrate dense tissues, and facility for genetic manipulation, their application in antivenoms has expanded considerably. VHHs that are active against the metalloprotease BjussuMP-II from the snake Bothrops jararacussu were selected. After isolation of BjussuMP-II, a camelid was immunized with the purified toxin in order to construct the recombinant phage library. Following a round of biopanning, 52% of the selected clones were able to recognize BjussuMP-II in an ELISA assay. After sequencing, seven sequence profiles were identified. One selected clone (VHH61) showed cross-reactivity to B. brazili venom, but did not recognize the Crotalus and Lachesis genera, indicating specificity for the Bothrops genus. Through in vitro tests, the capacity to neutralize the toxicity triggered by BjussuMP-II was observed. Circular dichroism spectroscopy indicated a robust secondary structure for VHH61, and the calculated melting temperature ( T M ) for the clone was 56.4°C. In silico analysis, through molecular docking of anti-BjussuMP-II VHHs with metalloprotease, revealed their potential interaction with amino acids present in regions critical for the toxin's conformation and stability. The findings suggest that anti-BjussuMP-II VHHs may be beneficial in the development of next-generation antivenoms., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Marcela C. S. Silva et al.)

Through active surveillance and contact tracing from outpatients, we aimed to identify and characterize SARS-CoV-2 variants circulating in Porto Velho-Rondônia, a city in the Brazilian Amazon. As part of a prospective cohort, we gathered information from 2,506 individuals among COVID-19 patients and household contacts. Epidemiological data, nasopharyngeal swabs, and blood samples were collected from all participants. Nasopharyngeal swabs were tested for antigen rapid diagnostic test and reverse transcription-polymerase chain reaction (RT-PCR) followed by genomic sequencing. Blood samples underwent ELISA testing for IgA, IgG, and IgM antibody levels. From 757 specimens sequenced, three were identified as Mu variant, none of the individuals carrying this variant had a travel history in the previous 15 days before diagnosis. One case was asymptomatic and two presented mild symptoms. Two infected individuals from different households caring viruses with additional amino acid substitutions ORF7a P45L and ORF1a T1055A compared to the Mu virus reference sequence. One patient presented IgG levels. Our results highlight that genomic surveillance for SARS-CoV-2 variants can assist in detecting the emergency of SARS-CoV-2 variants in the community, before its identification in other parts of the country., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Metabolomics emerged as an important tool to gain insights on how the body responds to therapeutic interventions. Bariatric surgery is the most effective treatment for severe obesity and obesity-related co-morbidities. Our aim was to conduct a systematic review of the available data on metabolomics profiles that characterize patients submitted to different bariatric surgery procedures, which could be useful to predict clinical outcomes including weight loss and type 2 diabetes remission. For that, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA guidelines were followed. Data from forty-seven original study reports addressing metabolomics profiles induced by bariatric surgery that met eligibility criteria were compiled and summarized. Amino acids, lipids, energy-related and gut microbiota-related were the metabolite classes most influenced by bariatric surgery. Among these, higher pre-operative levels of specific lipids including phospholipids, long-chain fatty acids and bile acids were associated with post-operative T2D remission. As conclusion, metabolite profiling could become a useful tool to predict long term response to different bariatric surgery procedures, allowing more personalized interventions and improved healthcare resources allocation., (© 2021. The Author(s).)

The differential diagnosis between adrenocortical adenomas (ACAs) and adrenocortical carcinomas (ACCs) relies on unspecific clinical, imaging and histological features, and, so far, no single molecular biomarker has proved to improve diagnostic accuracy. Similarly, prognostic factors have an insufficient capacity to predict the heterogeneity of ACC clinical outcomes, which consequently lead to inadequate treatment strategies. Angiogenesis is a biological process regulated by multiple signaling pathways, including VEGF and the Ang-Tie pathway. Many studies have stressed the importance of angiogenesis in cancer development and metastasis. In the present study, we evaluated the expression of VEGF and Ang-Tie pathway mediators in adrenocortical tumors (ACTs), with the ultimate goal of assessing whether these molecules could be useful biomarkers to improve diagnostic accuracy and/or prognosis prediction in ACC. The expression of the proteins involved in angiogenesis, namely CD34, VEGF, VEGF-R2, Ang1, Ang2, Tie1 and Tie2, was assessed by immunohistochemistry in ACC ( n = 22), ACA with Cushing syndrome ( n = 8) and non-functioning ACA ( n = 13). ACC presented a significantly higher Ang1 and Ang2 expression when compared to ACA. Tie1 expression was higher in ACC with venous invasion and in patients with shorter overall survival. In conclusion, although none of these biomarkers showed to be useful for ACT diagnosis, the Ang-Tie pathway is active in ACT and may play a role in regulating ACT angiogenesis.

COVID-19 is an intriguing infectious condition with multisystemic manifestations and variable outcomes that are influenced by the concomitant presence of non-communicable diseases, such as obesity, diabetes, and cardiovascular disease, which were previously well established epidemics and therefore are considered global syndemics. Although an enormous progress towards understanding mechanisms of SARS-CoV-2 infection leading to COVID-19 has been made, there are still many areas of uncertainty to clarify. Systemic diseases are characterized by common links that allow integrating apparently unrelated disease manifestations. The authors launch the provocative hypothesis that serotonin is the putative mediator linking the lung, gut, cardiac, neurological, and other systemic manifestations that characterize severe COVID-19 in individuals with diabetes and obesity. In support of a role for serotonin in the mechanisms leading to disease severity are the similarities between acute and post-acute COVID-19 manifestations and neuroendocrine tumors presenting with carcinoid syndrome. Scientific discussion is set by highlighting the available clues that support this working hypothesis to trigger future research aimed at unravelling the molecular pathways underlying SARS-CoV-2 infection that are still far from being fully disclosed., (© 2022 S. Karger AG, Basel.)

Monoclonal antibodies have contributed to improving the treatment of several diseases. However, limitations related to pharmacokinetic parameters and production costs have instigated the search for alternative products. Camelids produce functional immunoglobulins G devoid of light chains and CH1 domains, in which the antigenic recognition site is formed by a single domain called VHH or nanobody. VHHs' small size and similarity to the human VH domain contribute to high tissue penetration and low immunogenicity. In addition, VHHs provide superior antigen recognition compared to human antibodies, better solubility and stability. Due to these characteristics and the possibility of obtaining gene-encoding VHHs, applications of this biological tool, whether as a monomer or in related recombinant constructs, have been reported. To ensure antibody efficacy and cost-effectiveness, strategies for their expression, either using prokaryotic or eukaryotic systems, have been utilized. Plant-based expression systems are useful for VHH related constructs that require post-translational modifications. This system has exhibited versatility, low-cost upstream production, and safety. This article presents the main advances associated to the heterologous expression of VHHs in plant systems. Besides, we show insights related to the use of VHHs as a strategy for plant pathogen control and a tool for genomic manipulation in plant systems., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This study aimed to compare left ventricular outflow tract (LVOT) diameter measurements using two-dimensional (2D) echocardiography at the sino-tubular junction (STJ) and at the aortic valve (AV) hinges in newborn infants., Study Design: This is a retrospective study in a tertiary neonatal unit where infants underwent echocardiography for evaluation of murmur or as part of cardiovascular assessment. Three consecutive cardiac cycles were chosen to measure the LVOT diameter in end systole at the STJ and at the AV hinges. Bias and levels of agreement were examined using Bland-Altman plot. Intraobserver variability was examined using intraclass correlation., Results: A total of 366 measurements were obtained from 61 infants with a mean (standard deviation) gestation and birth weight of 33.4 (6.9) weeks and 2,181 (1369) g, respectively. There was good correlation between the LVOT diameter measurements using the STJ and AV hinges ( r  = 0.958, p  < 0.001). The mean (standard deviation and 95% confidence interval) bias between LVOT diameter measurements using STJ and AV hinges were 0.93 (0.45 and 0.06-1.81) mm. There was good intraobserver variability between the measurements using both methods., Conclusion: Using 2D echocardiography, LVOT measurements using the STJ tend to be higher when compared with LVOT measurements using the AV hinges., Key Points: · Echocardiographic assessment of left ventricular output is undertaken frequently.. · Left ventricular outflow tract can be measured at the aortic valve hinges, sinus of valsalva, or sino-tubular junction.. · Left ventricular outflow tract measured at the sino-tubular junction tends to higher when compared with aortic valve., Competing Interests: None declared., (Thieme. All rights reserved.)

The development of adjuvant therapies for obesity treatment is justified by the high prevalence of this disease worldwide, and the relationship between obesity and intestinal microbiota is a promising target for obesity treatment. Therefore, this study aimed at investigating the adjuvant treatment of obesity through the use of potential probiotics and antibiotics, either separately or sequentially. In the first phase of the experiment, animals had diet-induced obesity with consumption of a high saturated fat diet and a fructose solution. After this period, there was a reduction in caloric supply, that is the conventional treatment of obesity, and the animals were divided into 5 experimental groups: control group (G1), obese group (G2), potential probiotic group (G3), antibiotic group (G4), and antibiotic followed by potential probiotic group (G5). The adjuvant treatments lasted 4 weeks and were administered daily, via gavage: Animals in G1 and G2 received distilled water, the G3 obtained Lactobacillus gasseri LG-G12, and the G4 received ceftriaxone. The G5 received ceftriaxone for 2 weeks, followed by the offer of Lactobacillus gasseri LG-G12 for another 2 weeks. Parameters related to obesity, such as biometric measurements, food consumption, biochemical tests, histological assessments, short-chain fatty acids concentration, and composition of the intestinal microbiota, were analyzed. The treatment with caloric restriction and sequential supply of antibiotics and potential probiotics was able to reduce biometric measures, increase brown adipose tissue, and alter the intestinal microbiota phyla, standing out as a promising treatment for obesity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The aim of this study was to achieve greater specificity of dengue virus (DENV) serological tests based on a recombinant antigen derived from non-structural protein 1 (ΔNS1) with regard to cross-reactive Zika virus (ZIKV) anti-NS1 antibody responses. This is of relevance in endemic regions for the serological discrimination of both DENV and ZIKV, such as Brazil and other tropical countries., Methods: The ΔNS1 proteins were obtained as recombinant antigens and were evaluated as solid-phase-bound antigens in the ELISA test to detect anti-NS1 IgG antibodies. The performance of the ∆NS1-based DENV IgG ELISA was assessed with both mouse and human serum samples previously exposed to DENV or ZIKV., Results: The ∆NS1-based DENV IgG ELISA detected anti-DENV NS1 IgG without cross-reactivity with ZIKV-positive serum samples. The sensitivity and specificity of the assay determined using samples previously characterized by real-time PCR (qRT-PCR) or plaque reduction neutralization assay (PRNT) were 82% and 93%, respectively., Conclusion: The ∆NS1-based DENV IgG ELISA conferred enhanced diagnostic specificity for anti-DENV serological tests and may be particularly useful for serological analyses in endemic regions for both DENV and ZIKV transmission., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyze the production of meanings on interventions considered as Harm Reduction in the discourses of nursing professionals working in Primary Health Care., Method: Qualitative study based on the theoretical-methodological framework of French Discourse Analysis. Semi-structured interviews were conducted with 14 nursing professionals working in Primary Health Care, from February to October 2019., Results: Most Harm Reduction practices performed by nursing professionals aim to minimize risks and physical damage. Harm Reduction actions that require welcoming, non-judgment and qualified listening were observed. Some nursing professionals perform Harm Reduction actions, but do not recognize them as such., Conclusion: The production of meanings in the discourses of nursing professionals presented evidence of biomedical and/or disease discursive formations, health prevention, interpersonal relationships and health promotion.