A new trypsin inhibitor from Centrosema plumieri effective against digestive proteases from Tribolium castaneum, an eco-friendly alternative.

Tribolium castaneum, also known as the red flour beetle, is a polyphagous pest that seriously damages agricultural products, including stored and processed grains. Researchers have aimed to discover alternative pest control mechanisms that are less harmful to the ecosystem than those currently used. We conduct the purification and characterization of a protease inhibitor from C. plumieri seeds and an in vitro evaluation of its insecticidal potential against the insect pest T. castaneum. The trypsin inhibitor was isolated from C. plumieri seeds in a single-step DEAE-Sepharose column chromatography and had a molecular mass of 50 kDA. When analyzed for interaction with different proteolytic enzymes, the inhibitor exhibited specificity against trypsin and no activity against other serine proteases such as chymotrypsin and elastase-2. The isolated inhibitor was able to inhibit digestive enzymes of T. castaneum from extracts of the intestine of this insect. Therefore, we conclude that the new protease inhibitor, specific in tryptic inhibition, of protein nature from the seeds of C. plumieri was effective in inhibiting the digestive enzymes of T. castaneum and is a promising candidate in the ecological control of pests.

Wall enhancement as a biomarker of intracranial aneurysm instability: a histo-radiological study.

BACKGROUND: The aim of this is to explore the histological basis of vessel wall enhancement (WE) on magnetic resonance imaging (MRI), which is a strong radiological biomarker of aneurysmal prone to rupture compared to other classical risk predictors (e.g., PHASES score, size, morphology). METHODS: A prospective observational study was performed including all consecutive patients presenting with a saccular intracranial aneurysm at Vall d'Hebron University Hospital between October 2017 and May 2019. The patients underwent high-resolution 3 T MRI, and their aneurysms were classified into asymptomatic, symptomatic, and ruptured. A histological and immunohistochemical study was performed in a subgroup of patients (n = 20, of which 15 presented with WE). Multiple regression analyses were performed to identify predictors of rupture and aneurysm symptoms. RESULTS: A total of 132 patients were enrolled in the study. WE was present in 36.5% of aneurysms: 22.9% asymptomatic, 76.9% symptomatic, and 100% ruptured. Immunohistochemical markers associated with WE were CD3 T cell receptor (p = 0.05) and CD45 leukocyte common antigen (p = 0.05). Moreover, WE is an independent predictor of symptomatic and ruptured aneurysms (p < 0.001). CONCLUSIONS: Aneurysms with WE present multiple histopathological changes that may contribute to wall disruption and represent the pathophysiological basis of radiological WE. Moreover, WE is an independent diagnostic predictor of aneurysm symptoms and rupture.

Assessment of automatic decision-support systems for detecting active T2 lesions in multiple sclerosis patients.

BACKGROUND: Active (new/enlarging) T2 lesion counts are routinely used in the clinical management of multiple sclerosis. Thus, automated tools able to accurately identify active T2 lesions would be of high interest to neuroradiologists for assisting in their clinical activity. OBJECTIVE: To compare the accuracy in detecting active T2 lesions and of radiologically active patients based on different visual and automated methods. METHODS: One hundred multiple sclerosis patients underwent two magnetic resonance imaging examinations within 12 months. Four approaches were assessed for detecting active T2 lesions: (1) conventional neuroradiological reports; (2) prospective visual analyses performed by an expert; (3) automated unsupervised tool; and (4) supervised convolutional neural network. As a gold standard, a reference outcome was created by the consensus of two observers. RESULTS: The automated methods detected a higher number of active T2 lesions, and a higher number of active patients, but a higher number of false-positive active patients than visual methods. The convolutional neural network model was more sensitive in detecting active T2 lesions and active patients than the other automated method. CONCLUSION: Automated convolutional neural network models show potential as an aid to neuroradiological assessment in clinical practice, although visual supervision of the outcomes is still required.

Assessment of 2D conventional and synthetic MRI in multiple sclerosis.

PURPOSE: To qualitatively and quantitatively compare synthetic and conventional MRI sequences acquired on a 1.5-T system for patients with multiple sclerosis (MS). METHODS: Prospective study that involved twenty-seven consecutive relapsing-remitting MS patients scanned on a 1.5-T MRI scanner. The MRI protocol included 2D transverse conventional spin-echo sequences: proton density-weighted (PD), T2-weighted, T2-FLAIR, and T1-weighted. Synthetic images were generated using 2D transverse QRAPMASTER and SyMRI software with the same voxel size, repetition, echo, and inversion times as the conventional sequences. Four raters performed a crosstab qualitative analysis that involved evaluating global image quality, contrast, flow artefacts, and confidence in lesion assessment introducing the concepts of predominance, agreement, and disagreement. A quantitative analysis was also performed and included evaluating the number of lesions (periventricular, juxtacortical, brainstem, and cerebellum) and the contrast-to-noise ratio between regions (CSF, white matter, grey matter, lesions). RESULTS: The global image quality assessment showed predominance for better scores for conventional sequences over synthetic sequences, whereas contrast, confidence in lesion assessment, and flow artefacts showed predominance for agreement between sequences. There was predominance for disagreement between all pairs of raters in most of the evaluated qualitative parameters. Synthetic PD and T2-FLAIR images showed higher contrast-to-noise ratios than the corresponding conventional images for most comparison between regions. There were no significant differences in the number of lesions detected for most of the study regions between conventional and synthetic images. CONCLUSION: Synthetic MRI can be potentially used as an alternative to conventional brain MRI sequences in the assessment of MS.

Structural and calorimetric studies reveal specific determinants for the binding of a high-affinity NLS to mammalian importin-alpha.

The classical nuclear import pathway is mediated by importin (Impα and Impß), which recognizes the cargo protein by its nuclear localization sequence (NLS). NLSs have been extensively studied resulting in different proposed consensus; however, recent studies showed that exceptions may occur. This mechanism may be also dependent on specific characteristics of different Impα. Aiming to better understand the importance of specific residues from consensus and adjacent regions of NLSs, we studied different mutations of a high-affinity NLS complexed to Impα by crystallography and calorimetry. We showed that although the consensus sequence allows Lys or Arg residues at the second residue of a monopartite sequence, the presence of Arg is very important to its binding in major and minor sites of Impα. Mutations in the N or C-terminus (position P1 or P6) of the NLS drastically reduces their affinity to the receptor, which is corroborated by the loss of hydrogen bonds and hydrophobic interactions. Surprisingly, a mutation in the far N-terminus of the NLS led to an increase in the affinity for both binding sites, corroborated by the structure with an additional hydrogen bond. The binding of NLSs to the human variant Impα1 revealed that these are similar to those found in structures presented here. For human variant Impα3, the bindings are only relevant for the major site. This study increases understanding of specific issues sparsely addressed in previous studies that are important to the task of predicting NLSs, which will be relevant in the eventual design of synthetic NLSs.

The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS.

OBJECTIVE: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. METHODS: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). RESULTS: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. CONCLUSION: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS.

Texture analysis in susceptibility-weighted imaging may be useful to differentiate acute from chronic multiple sclerosis lesions.

OBJECTIVES: To evaluate the diagnostic performance of texture analysis (TA) applied on non-contrast-enhanced susceptibility-weighted imaging (SWI) to differentiate acute (enhancing) from chronic (non-enhancing) multiple sclerosis (MS) lesions. METHODS: We analyzed 175 lesions from 58 patients with relapsing-remitting MS imaged on a 3.0 T MRI scanner and applied TA on T2-w and SWI images to extract texture features. We evaluated the presence or absence of lesion enhancement on T1-w post-contrast images and performed a computational statistical analysis to assess if there was any significant correlation between the texture features and the presence of lesion activity. ROC curves and leave-one-out cross-validation were used to evaluate the performance of individual features and multiparametric models in the identification of active lesions. RESULTS: Multiple TA features obtained from SWI images showed a significantly different distribution in acute and chronic lesions (AUC, 0.617-0.720). Multiparametric predictive models based on logistic ridge regression and partial least squares regression yielded an AUC of 0.778 and 0.808, respectively. Results from T2-w images did not show any significant predictive ability of neither individual features nor multiparametric models. CONCLUSIONS: Texture analysis on SWI sequences may be useful to differentiate acute from chronic MS lesions. The good diagnostic performance could help to reduce the need of intravenous contrast agent administration in follow-up MRI studies. KEY POINTS: • Texture analysis applied on SWI sequences may be useful to differentiate acute from chronic multiple sclerosis lesions • The good diagnostic performance could help to minimize the need of intravenous contrast agent administration in follow-up MRI studies.

The value of oligoclonal bands in the multiple sclerosis diagnostic criteria.

The presence of oligoclonal bands in clinically isolated syndromes is an independent risk factor for developing multiple sclerosis and has been largely excluded from the more recent multiple sclerosis diagnostic criteria. Therefore, our objective was to explore the value of oligoclonal bands in the context of the 2010 McDonald criteria, especially in patients fulfilling exclusively dissemination in space at baseline. For this purpose, we selected 566 patients from a clinically isolated syndrome inception cohort who had IgG oligoclonal bands determination and sufficient data on baseline brain MRI to assess dissemination in space and time. We excluded the cases already fulfilling both dissemination in space and time and divided the remaining 398 into 'no dissemination in space and time' (n = 218), 'dissemination in space' (n = 164) and 'dissemination in time' (n = 16). We assessed Cox proportional hazards regression models with 2010 McDonald as the outcome, using 'no dissemination in space and time' with 0 lesions and negative oligoclonal bands as the reference for different subgroups according to oligoclonal bands status (positive/negative). To assess the diagnostic properties, we selected cases with a follow-up ≥3 years or fulfilling 2010 McDonald within 3 years of the clinically isolated syndrome (n = 314), and compared the performance of all 'dissemination in space' cases (n = 137) versus patients with 'dissemination in space' and positive oligoclonal bands (n = 101). The remaining patients classified as fulfilling 'dissemination in time' or 'no dissemination in space and time' were taken into account to calculate the diagnostic properties. The respective adjusted hazard ratios (95% confidence interval) were 1.5 (0.4-5.7) for 'no dissemination in space and time' with 0 lesions and positive oligoclonal bands, 3.1 (1.4-7.2) for 'no dissemination in space and time' with ≥1 lesions and negative oligoclonal bands, 7.4 (3.5-15.7) for 'no dissemination in space and time' with ≥1 lesions and positive oligoclonal bands, 10.4 (4.8-22.6) for 'dissemination in space' with negative oligoclonal bands, 15.3 (7.5-31.3) for 'dissemination in space' with positive oligoclonal bands, and 9.1 (3.5-23.4) for 'dissemination in time' (not subdivided due to the sample size). The specificity for all cases with 'dissemination in space' was 80.6 and increased to 88.1 after selecting those with positive oligoclonal bands. According to these results, we propose radiological dissemination in space at any time plus positive oligoclonal bands as an additional criterion for diagnosing multiple sclerosis.

Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds.

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.

First pregnancy and live birth from ex vivo-retrieved metaphase II oocytes from a woman with bilateral ovarian carcinoma: a case report.

OBJECTIVE: To report pregnancy and live birth resulting from intracytoplasmic sperm injection of ex vivo-retrieved mature oocytes from a woman with bilateral ovarian carcinoma. DESIGN: Case report. SETTING: Fertility clinic. PATIENT: A 34-year-old nulliparous woman with bilateral ovarian tumor, with a risk of malignancy of 96.1% according to International Ovarian Tumor Analysis Group recommendations for adnexal tumors, who desired fertility preservation before definitive surgical treatment. INTERVENTION(S): Cryopreservation of ex vivo-retrieved mature metaphase II oocytes is followed by fertilization with donor sperm and embryo transfer to a gestational carrier. MAIN OUTCOME MEASURE(S): Fertility preservation. RESULTS: After controlled ovarian stimulation, 12 metaphase II oocytes were retrieved from oophorectomized specimens and vitrified. Intracytoplasmic sperm injection with donor sperm was performed in remission, resulting in 9 cleavage-stage embryos, 2 of which were transferred to a gestational carrier, resulting in a normal, healthy singleton pregnancy, and the live birth of a healthy infant. CONCLUSION(S): Ex vivo oocyte retrieval after oophorectomy may be a safe alternative to standard oocyte retrieval for fertility preservation in women with ovarian malignancies.

Adding the Optic Nerve in Multiple Sclerosis Diagnostic Criteria: A Longitudinal, Prospective, Multicenter Study

BACKGROUND AND OBJECTIVES: The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort. METHODS: MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome. RESULTS: We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% [with ON-MRI] vs 88.2%), but slightly lower specificity (80.0% [with GCIPL IEA ≥4 µm] vs 82.2%), with overall similar accuracy (86.6% [with ON-MRI] vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes. DISCUSSION: In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.

Structural basis of nuclear import of flap endonuclease 1 (FEN1).

Flap endonuclease 1 (FEN1) is a member of the nuclease family and is structurally conserved from bacteriophages to humans. This protein is involved in multiple DNA-processing pathways, including Okazaki fragment maturation, stalled replication-fork rescue, telomere maintenance, long-patch base-excision repair and apoptotic DNA fragmentation. FEN1 has three functional motifs that are responsible for its nuclease, PCNA-interaction and nuclear localization activities, respectively. It has been shown that the C-terminal nuclear localization sequence (NLS) facilitates nuclear localization of the enzyme during the S phase of the cell cycle and in response to DNA damage. To determine the structural basis of the recognition of FEN1 by the nuclear import receptor importin α, the crystal structure of the complex of importin α with a peptide corresponding to the FEN1 NLS was solved. Structural studies confirmed the binding of the FEN1 NLS as a classical bipartite NLS; however, in contrast to the previously proposed (354)KRKX(8)KKK(367) sequence, it is the (354)KRX(10)KKAK(369) sequence that binds to importin α. This result explains the incomplete inhibition of localization that was observed on mutating residues (365)KKK(367). Acidic and polar residues in the X(10) linker region close to the basic clusters play an important role in binding to importin α. These results suggest that the basic residues in the N-terminal basic cluster of bipartite NLSs may play roles that are more critical than those of the many basic residues in the C-terminal basic cluster.

Liver resection for hepatocellular carcinoma beyond the BCLC: are multinodular disease, portal hypertension, and portal system invasion real contraindications?

Background: Barcelona Clinic Liver Cancer (BCLC) is a recognized guideline to standardize treatment allocation for hepatocellular carcinoma (HCC); however, many centers criticize its restrictive liver resection recommendations and have published good results after more liberal hepatectomy indications. The objective is to evaluate the results of HCC resection in a single center, with a more liberal indication for resection than proposed by the BCLC guideline. It was performed a retrospective cohort study including all patients who underwent liver resection for HCC in a single center between April 2008 and November 2018. Methods: The results of 150 patients who underwent hepatectomy were evaluated and compared facing both 2010 and 2018 BCLC guidelines. Overall and disease-free survival after resection in patients with none, one, two, or three of the risk factors, as proposed by the BCLC, as contraindications to resection (portal hypertension, portal invasion, and more than one nodule) were analyzed. Results: Nodule size and presence of portal invasion alone did not affect prognosis. If the BCLC 2010 and 2018 guidelines were followed, 46.7% and 26.7% of the patients, respectively, would not have received potentially curative treatment. The median overall and disease-free survival for patients with one BCLC contraindication factor were 43.3 and 15.1 months, respectively. The presence of two risk factors had a negative impact on overall survival (OS) and disease-free survival (DFS), although some patients had long-term survival. The only patient with the three risk factors had a poor outcome. Conclusions: Selected patients with one BCLC contraindication factor may undergo resection with good results, whereas those with two factors should be allocated for hepatectomy only in favorable scenarios. Patients with the three risk factors do not appear to benefit from resection.

Knowledge of oral and oropharyngeal cancer by dental surgeons: an integrative review.

OBJECTIVES: to identify the evidence available in the literature on the knowledge of dentists regarding risk factors and early diagnosis of oral and oropharyngeal cancer. METHODS: it is an integrative review of the literature. Boolean descriptors and operators were searched in the PubMed and LILACS databases, using gray literature, in English, Spanish and Portuguese. RESULTS: of the 79 PubMed and 152 LILACS articles, 24 were selected. Of these, eight showed good knowledge of dentists, while most showed low or little knowledge of risk factors and early diagnosis in dentists. All studies, however, highlight the need for continuing education to improve and maintain knowledge about risk factors and early diagnosis. CONCLUSIONS: most dental surgeons have insufficient knowledge of oral/oropharyngeal cancer. Continued education is suggested, aiming at improving knowledge and early diagnosis.

MRI findings in cervical spondylotic myelopathy with gadolinium enhancement: Review of seven cases.

Cervical spondylotic myelopathy (CSM) is a clinical syndrome secondary to a spinal cord compression due to cervical spondylosis. In some cases, conventional MRI typically shows an intramedullary hyperintense signal on T2W imaging and contrast enhancement on post-gadolinium T1W imaging. We report a series of seven patients with CSM who had typical clinical presentation and imaging findings on T2W and contrast-enhanced T1W sequences. The imaging findings included degenerative changes of the cervical spine, intramedullary T2-signal hyperintensity, and an intramedullary enhancement on post-gadolinium T1W images. Our results support the statement that the presence of an intramedullary gadolinium-enhancement with a flat transverse pancake-like pattern (on sagittal images) and a circumferential pattern (on axial images), located within a T2-signal abnormality, in patients with cervical spondylosis and clinical myelopathy is indicative of spondylosis as the cause of the myelopathy.

Biochemical and biophysical characterization of the RVB-1/RVB-2 protein complex, the RuvBL/RVB homologues in Neurospora crassa.

The RVB proteins, composed of the conservative paralogs, RVB1 and RVB2, belong to the AAA+ (ATPases Associated with various cellular Activities) protein superfamily and are present in archaea and eukaryotes. The most distinct structural features are their ability to interact with each other forming the RVB1/2 complex and their participation in several macromolecular protein complexes leading them to be involved in many biological processes. We report here the biochemical and biophysical characterization of the Neurospora crassa RVB-1/RVB-2 complex. Chromatographic analyses revealed that the complex (APO) predominantly exists as a dimer in solution although hexamers were also observed. Nucleotides influence the oligomerization state, while ATP favors hexamers formation, ADP favors the formation of multimeric states, likely dodecamers, and the Molecular Dynamics (MD) simulations revealed the contribution of certain amino acid residues in the nucleotide stabilization. The complex binds to dsDNA fragments and exhibits ATPase activity, which is strongly enhanced in the presence of DNA. In addition, both GFP-fused proteins are predominantly nuclear, and their nuclear localization signals (NLS) interact with importin-α (NcIMPα). Our findings show that some properties are specific of the fungus proteins despite of their high identity to orthologous proteins. They are essential proteins in N. crassa, and the phenotypic defects exhibited by the heterokaryotic strains, mainly related to growth and development, indicate N. crassa as a promising organism to investigate additional biological and structural aspects of these proteins.

COVID-19: Short and Long-Term Effects of Hospitalization on Muscular Weakness in the Elderly.

The COVID-19 pandemic has recently been the cause of a global public health emergency. Frequently, elderly patients experience a marked loss of muscle mass and strength during hospitalization, resulting in a significant functional decline. This paper describes the impact of prolonged immobilization and current pharmacological treatments on muscular metabolism. In addition, the scientific evidence for an early strength intervention, neuromuscular electrical stimulation or the application of heat therapy during hospitalization to help prevent COVID-19 functional sequels is analyzed. This review remarks the need to: (1) determine which potential pharmacological interventions have a negative impact on muscle quality and quantity; (2) define a feasible and reliable pharmacological protocol to achieve a balance between desired and undesired medication effects in the treatment of this novel disease; (3) implement practical strategies to reduce muscle weakness during bed rest hospitalization and (4) develop a specific, early and safe protocol-based care of functional interventions for older adults affected by COVID-19 during and after hospitalization.

Comparative study of the interactions between fungal transcription factor nuclear localization sequences with mammalian and fungal importin-alpha.

Importin-α (Impα) is an adaptor protein that binds to cargo proteins (containing Nuclear Localization Sequences - NLSs), for their translocation to the nucleus. The specificities of the Impα/NLS interactions have been studied, since these features could be used as important tools to find potential NLSs in nuclear proteins or even for the development of targets to inhibit nuclear import or to design peptides for drug delivery. Few structural studies have compared different Impα variants from the same organism or Impα of different organisms. Previously, we investigated nuclear transport of transcription factors with Neurospora crassa Impα (NcImpα). Herein, NIT-2 and PAC-3 transcription factors NLSs were studied in complex with Mus musculus Impα (MmImpα). Calorimetric assays demonstrated that the PAC-3 NLS peptide interacts with both Impα proteins with approximately the same affinity. The NIT-2 NLS sequence binds with high affinity to the Impα major binding site from both organisms, but its binding to minor binding sites reveals interesting differences due to the presence of additional interactions of NIT-2-NLS with MmImpα. These findings, together with previous results with Impα from other organisms, indicate that the differential affinity of NLSs to minor binding sites may be also responsible for the selectivity of some cargo proteins recognition and transport.

Weight loss probiotic supplementation effect in overweight and obesity subjects: A review.

Obese individuals present adverse changes in the diversity and composition of the gut microbiota, leading to alterations in energy balance, lipid metabolism, endocrine disturbances, and low-grade chronic systemic inflammation increases. Probiotic supplementation appears to change gut microbiota by decrease gut permeability, inflammation, and metabolic disorders, creating a promising environment to weight loss. This revision resumes the main findings of probiotic supplementation and weight loss that contributed to building the current background linking changes in gut microbiota profile and with obesity.

construção de uma proposta de educação continuada sobre vacinação infantil para agentes comunitários de saúde / Construction of a continuing education proposal on childhood vaccination for community health agents / Construcción de una propuesta de educación continua sobre vacunación infantil para agentes comunitarios de salud

O objetivo deste estudo foi relatar a experiência do desenvolvimento de uma proposta de educação continuada executada pela equipe de enfermagem com agentes comunitários de saúde (ACS), considerando como foco a vacinação infantil. Trata-se de um relato de experiência elaborado e vivenciado por enfermeiro e acadêmico de enfermagem em novembro de 2019, com a participação de duas equipes pertencentes a uma Unidade Básica de Saúde do município de Arapiraca (AL). Através da metodologia de ensino da problematização por meio do Arco de Maguerez, foram realizadas oficinas e ações educativas para os ACS, a partir das necessidades relatadas por esses profissionais em relação à vacinação infantil. Tais atividades proporcionaram maior aproximação com a realidade vivenciada por quem ocupa a posição de educador e incentivador do cuidado da saúde durante a visita domiciliar. Além disso, enfatizaram a importância do enfermeiro enquanto responsável pela educação continuada da equipe. Verificou-se ainda que o diálogo aberto e horizontal, de modo empático, proporcionou a construção de uma ferramenta eficaz, de fácil manuseio e de baixo custo, que gerou uma melhor memorização e segurança não somente para os ACS nas visitas domiciliares, mas também nas atividades de outros profissionais atuantes no campo da promoção da saúde infantil.

This study reports the experience of developing an educational product based on continued education carried out by a nursing team with community health agents (CHA) considering childhood vaccination as the focus. This is an experience report that was prepared and experienced by a nurse and nursing student in November 2019, with the participation of two teams belonging to a basic health unit in the municipality of Arapiraca, Alagoas, Brazil. Using the problematization teaching methodology by Arco de Marguerez, workshops and educational actions were carried out for the CHA based on the needs they reported regarding childhood vaccination, which provided a greater approximation with the reality experienced by those in the position of educators and encouragers of health care during home visits. Furthermore, it emphasized the importance of nurses as responsible for the team's continuing education. It was also verified that open and horizontal dialogue empathetically provided the construction of an effective, easy to use, low cost tool, bringing better memorization and safety not only for community agents during home visits but also in activities from other professionals working in the field of child health promotion.

El objetivo de este estudio fue reportar la experiencia de desarrollo de una propuesta de educación continua realizada por el equipo de enfermería con agentes comunitarios de salud (ACS), considerando como enfoque la vacunación infantil. Este es un reporte de experiencia elaborado y vivido por un enfermero y un estudiante de enfermería en noviembre de 2019, con la participación de dos equipos de una unidad básica de salud de la ciudad de Arapiraca, Brasil. Utilizando la metodología de enseñanza de problematización del Arco de Maguerez, se realizaron talleres y acciones educativas para ACS a partir de las necesidades reportadas por estos profesionales con relación a la vacunación infantil. Estas actividades proporcionaron una mayor aproximación a la realidad vivida por quienes ocupan la posición de educador y motivador del cuidado de la salud durante la visita domiciliaria. Además, destacaron la importancia del enfermero como responsable de la formación continua del equipo. También se constató que el diálogo abierto y horizontal, de manera empática, propició la construcción de una herramienta efectiva, fácil de usar y de bajo costo, que generó una mejor memorización y seguridad no solo para los ACS durante las visitas domiciliarias, sino también en las actividades de otros profesionales que trabajan en el campo de la promoción de la salud infantil.