Transdiaphragmatic intercostal hernia induced by sternutation: A case report.

INTRODUCTION AND IMPORTANCE: Sternutation is, by definition, a situation that increases abdominal pressure. However, it has not been clearly linked to protrusion of abdominal content through weaknesses in the abdominal boundaries. CASE PRESENTATION: Here we present a case report in which the only trigger factor found for an abdominal content protrusion was a sternutation episode. The patient arrived in our institution with the diagnosis of a transdiaphragmatic intercostal hernia, proven in CT-scan. He was, then, submitted to emergent surgery, where through thoracotomy and subcostal laparotomy, hernia content was reduced. The patient had a favorable evolution. CLINICAL DISCUSSION: TDIH is a rare entity, for which there are still no consensus regarding its management. This makes clinical practice more challenging, leaving to the surgeon the therapeutic decision tailored to each patient. CONCLUSION: This entity should be further studied, and consensus reached regarding its management.

Economic and Accessible Portable Homemade Magnetic Hyperthermia System: Influence of the Shape, Characteristics and Type of Nanoparticles in Its Effectiveness.

Currently, one of the main causes of death in the world is cancer; therefore, it is urgent to obtain a precocious diagnosis, as well as boost research and development of new potential treatments, which should be more efficient and much less invasive for the patient. Magnetic hyperthermia (MH) is an emerging cancer therapy using nanoparticles, which has proved to be effective when combined with chemotherapy, radiotherapy and/or surgery, or even by itself, depending on the type and location of the tumor's cells. This article presents the results obtained by using a previously developed economic homemade hyperthermia device with different types of magnetite nanoparticles, with sizes ranging between 12 ± 5 and 36 ± 11 nm and presenting different shapes (spherical and cubic particles). These magnetic nanoparticles (MNPs) were synthesized by three different methods (co-precipitation, solvothermal and hydrothermal processes), with their final form being naked, or possessing different kinds of covering layers (polyethylene glycol (PEG) or citric acid (CA)). The parameters used to characterize the heating by magnetic hyperthermia, namely the Specific Absorption Rate (SAR) and the intrinsic loss power (ILP), have been obtained by two different methods. Among other results, these experiments allowed for the determination of which synthesized MNPs showed the best performance concerning hyperthermia. From the results, it may be concluded that, as expected, the shape of MNPs is an important factor, as well as the time that the MNPs can remain suspended in solution (which is directly related to the concentration and covering layer of the MNPs). The MNPs that gave the best results in terms of the SAR were the cubic particles covered with PEG, while in terms of total heating the spherical particles covered with citric acid proved to be better.

Comparison among Different Green Extraction Methods of Polyphenolic Compounds from Exhausted Olive Oil Pomace and the Bioactivity of the Extracts.

The use of by-products as a source of bioactive compounds with economic added value is one of the objectives of a circular economy. The olive oil industry is a source of olive pomace as a by-product. The olive pomace used in the present study was the exhausted olive pomace, which is the by-product generated from the air drying and subsequent hexane extraction of residual oil from the olive pomace. The objective was to extract bioactive compounds remaining in this by-product. Various types of green extraction were used in the present study: solvent extraction (water and hydroalcoholic); ultrasound-assisted extraction; Ultra-Turrax-assisted extraction; and enzyme-assisted extraction (cellulase; viscoenzyme). The phenolic profile of each extract was determined using HPLC-DAD and the total phenolic content (TPC) and antioxidant activity (ABTS, DPPH, and ORAC) were determined as well. The results showed significant differences in the yield of extraction among the different methods used, with the enzyme-assisted, with or without ultrasound, extraction presenting the highest values. The ultrasound-assisted hydroethanolic extraction (USAHE) was the method that resulted in the highest content of the identified phenolic compounds: 2.021 ± 0.29 mg hydroxytyrosol/100 mg extract, 0.987 ± 0.09 mg tyrosol/100 mg extract, and 0.121 ± 0.005 mg catechol/100 mg extract. The conventional extraction with water at 50 °C produced the best results for TPC and antioxidant activity of the extracts. The extracts from the USAHE were able to inhibit Gram-positive bacteria, especially Bacillus cereus, showing 67.2% inhibition at 3% extract concentration.

High-Pressure Processing Effects on Microbiological Stability, Physicochemical Properties, and Volatile Profile of a Fruit Salad.

Nowadays, consumers are more aware of the effects of their diet on their health, and thus demand natural or minimally processed food products. Therefore, research has focused on processes that assure safe products without jeopardizing their nutritional properties. In this context, this work aimed to evaluate the effects of high-pressure processing (550 MPa/3 min/15 °C, HPP) on a fruit salad (composed of melon juice and pieces of Golden apple and Rocha pear) throughout 35 days of storage at 4 °C. For the physicochemical properties analysed (browning degree, polyphenol oxidase activity, antioxidant activity (ABTS assay), and volatile profile), a freshly made fruit salad was used, while for the microbiological tests (total aerobic mesophiles, and yeast and moulds) spoiled melon juice was added to the fruit salad to increase the microbial load and mimic a challenge test with a high initial microbial load. It was determined that processed samples were more microbiologically stable than raw samples, as HPP enabled a reduction of almost 4-log units of both total aerobic mesophiles and yeasts and moulds, as well as an almost 1.5-fold increase in titratable acidity of the unprocessed samples compared to HPP samples. Regarding browning degree, a significant increase (p < 0.05) was observed in processed versus unprocessed samples (roughly/maximum 68%), while the addition of ascorbic acid decreased the browning of the samples by 29%. For antioxidant activity, there were no significant differences between raw and processed samples during the 35 days of storage. An increase in the activity of polyphenol oxidase immediately after processing (about 150%) was confirmed, which was generally similar or higher during storage compared with the raw samples. Regarding the volatile profile of the product, it was seen that the compounds associated with melon represented the biggest relative percentage and processed samples revealed a decrease in the relative quantity of these compounds compared to unprocessed. Broadly speaking, HPP was shown to be efficient in maintaining the stability and overall quality of the product while assuring microbial safety (by inactivating purposely inoculated microorganisms), which allows for longer shelf life (7 versus 28 days for unprocessed and processed fruit salad, respectively).

Targeting pediatric cancers via T-cell recognition of the monomorphic MHC class I-related protein MR1.

Human leukocyte antigen (HLA) restriction of conventional T-cell targeting introduces complexity in generating T-cell therapy strategies for patients with cancer with diverse HLA-backgrounds. A subpopulation of atypical, major histocompatibility complex-I related protein 1 (MR1)-restricted T-cells, distinctive from mucosal-associated invariant T-cells (MAITs), was recently identified recognizing currently unidentified MR1-presented cancer-specific metabolites. It is hypothesized that the MC.7.G5 MR1T-clone has potential as a pan-cancer, pan-population T-cell immunotherapy approach. These cells are irresponsive to healthy tissue while conferring T-cell receptor(TCR) dependent, HLA-independent cytotoxicity to a wide range of adult cancers. Studies so far are limited to adult malignancies. Here, we investigated the potential of MR1-targeting cellular therapy strategies in pediatric cancer. Bulk RNA sequencing data of primary pediatric tumors were analyzed to assess MR1 expression. In vitro pediatric tumor models were subsequently screened to evaluate their susceptibility to engineered MC.7.G5 TCR-expressing T-cells. Targeting capacity was correlated with qPCR-based MR1 mRNA and protein overexpression. RNA expression of MR1 in primary pediatric tumors varied widely within and between tumor entities. Notably, embryonal tumors exhibited significantly lower MR1 expression than other pediatric tumors. In line with this, most screened embryonal tumors displayed resistance to MR1T-targeting in vitro MR1T susceptibility was observed particularly in pediatric leukemia and diffuse midline glioma models. This study demonstrates potential of MC.7.G5 MR1T-cell immunotherapy in pediatric leukemias and diffuse midline glioma, while activity against embryonal tumors was limited. The dismal prognosis associated with relapsed/refractory leukemias and high-grade brain tumors highlights the promise to improve survival rates of children with these cancers.

Olive oil nanoemulsion containing curcumin: antimicrobial agent against multidrug-resistant bacteria.

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.

Implicit bias in diagnosing mosaicism amongst preimplantation genetic testing providers: results from a multicenter study of 36 395 blastocysts.

STUDY QUESTION: Does the diagnosis of mosaicism affect ploidy rates across different providers offering preimplantation genetic testing for aneuploidies (PGT-A)? SUMMARY ANSWER: Our analysis of 36 395 blastocyst biopsies across eight genetic testing laboratories revealed that euploidy rates were significantly higher in providers reporting low rates of mosaicism. WHAT IS KNOWN ALREADY: Diagnoses consistent with chromosomal mosaicism have emerged as a third category of possible embryo ploidy outcomes following PGT-A. However, in the era of mosaicism, embryo selection has become increasingly complex. Biological, technical, analytical, and clinical complexities in interpreting such results have led to substantial variability in mosaicism rates across PGT-A providers and clinics. Critically, it remains unknown whether these differences impact the number of euploid embryos available for transfer. Ultimately, this may significantly affect clinical outcomes, with important implications for PGT-A patients. STUDY DESIGN, SIZE, DURATION: In this international, multicenter cohort study, we reviewed 36 395 consecutive PGT-A results, obtained from 10 035 patients across 11 867 treatment cycles, conducted between October 2015 and October 2021. A total of 17 IVF centers, across eight PGT-A providers, five countries and three continents participated in the study. All blastocysts were tested using trophectoderm biopsy and next-generation sequencing. Both autologous and donation cycles were assessed. Cycles using preimplantation genetic testing for structural rearrangements were excluded from the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The PGT-A providers were randomly categorized (A to H). Providers B, C, D, E, F, G, and H all reported mosaicism, whereas Provider A reported embryos as either euploid or aneuploid. Ploidy rates were analyzed using multilevel mixed linear regression. Analyses were adjusted for maternal age, paternal age, oocyte source, number of embryos biopsied, day of biopsy, and PGT-A provider, as appropriate. We compared associations between genetic testing providers and PGT-A outcomes, including the number of chromosomally normal (euploid) embryos determined to be suitable for transfer. MAIN RESULTS AND THE ROLE OF CHANCE: The mean maternal age (±SD) across all providers was 36.2 (±5.2). Our findings reveal a strong association between PGT-A provider and the diagnosis of euploidy and mosaicism. Amongst the seven providers that reported mosaicism, the rates varied from 3.1% to 25.0%. After adjusting for confounders, we observed a significant difference in the likelihood of diagnosing mosaicism across providers (P < 0.001), ranging from 6.5% (95% CI: 5.2-7.4%) for Provider B to 35.6% (95% CI: 32.6-38.7%) for Provider E. Notably, adjusted euploidy rates were highest for providers that reported the lowest rates of mosaicism (Provider B: euploidy, 55.7% (95% CI: 54.1-57.4%), mosaicism, 6.5% (95% CI: 5.2-7.4%); Provider H: euploidy, 44.5% (95% CI: 43.6-45.4%), mosaicism, 9.9% (95% CI: 9.2-10.6%)); and Provider D: euploidy, 43.8% (95% CI: 39.2-48.4%), mosaicism, 11.0% (95% CI: 7.5-14.5%)). Moreover, the overall chance of having at least one euploid blastocyst available for transfer was significantly higher when mosaicism was not reported, when we compared Provider A to all other providers (OR = 1.30, 95% CI: 1.13-1.50). Differences in diagnosing and interpreting mosaic results across PGT-A laboratories raise further concerns regarding the accuracy and relevance of mosaicism predictions. While we confirmed equivalent clinical outcomes following the transfer of mosaic and euploid blastocysts, we found that a significant proportion of mosaic embryos are not used for IVF treatment. LIMITATIONS, REASONS FOR CAUTION: Due to the retrospective nature of the study, associations can be ascertained, however, causality cannot be established. Certain parameters such as blastocyst grade were not available in the dataset. Furthermore, certain platform-related and clinic-specific factors may not be readily quantifiable or explicitly captured in our dataset. As such, a full elucidation of all potential confounders accounting for variability may not be possible. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the strong need for standardization and quality assurance in the industry. The decision not to transfer mosaic embryos may ultimately reduce the chance of success of a PGT-A cycle by limiting the pool of available embryos. Until we can be certain that mosaic diagnoses accurately reflect biological variability, reporting mosaicism warrants utmost caution. A prudent approach is imperative, as it may determine the difference between success or failure for some patients. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Torres Quevedo Grant, awarded to M.P. (PTQ2019-010494) by the Spanish State Research Agency, Ministry of Science and Innovation, Spain. M.P., L.B., A.R.L., A.L.R.d.C.L., N.P.P., M.P., D.S., F.A., A.P., B.M., L.D., F.V.M., D.S., M.R., E.P.d.l.B., A.R., and R.V. have no competing interests to declare. B.L., R.M., and J.A.O. are full time employees of IB Biotech, the genetics company of the Instituto Bernabeu group, which performs preimplantation genetic testing. M.G. is a full time employee of Novagen, the genetics company of Cegyr, which performs preimplantation genetic testing. TRIAL REGISTRATION NUMBER: N/A.

Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes

Abstract Objective: To examine whether the DDAH2 promoter polymorphisms -1415G/A (rs2272592), -1151A/C (rs805304) and -449G/C (rs805305), and their haplotypes, are associated with PE compared with normotensive pregnant women, and whether they affect ADMA levels in these groups. Methods: A total of 208 pregnant women were included in the study and classified as early-onset (N=57) or late-onset PE (N =49), and as normotensive pregnant women (N = 102). Results: Pregnant with early-onset PE carrying the GC and GG genotypes for the DDAH2 -449G/C polymorphism had increased ADMA levels (P=0.01). No association of DDAH2 polymorphisms with PE in single-locus analysis was found. However, the G-C-G haplotype was associated with the risk for late-onset PE. Conclusion: It is suggested that DDAH2 polymorphisms could affect ADMA levels in PE, and that DDAH2 haplotypes may affect the risk for PE.

Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão / G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.

Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Pediatric chronic kidney disease: blood cell count indexes as inflammation markers / Doença renal crônica pediátrica: índices de contagem de células sanguíneas como marcadores de inflamação

Abstract Introduction: Chronic kidney disease (CKD) is defined as a progressive decline of kidney functions. In childhood, the main triggering factors are congenital anomalies of the kidneys and urinary tract (CAKUT) and glomerulopathies. Inflammatory responses present challenges for diagnosis and staging, which justifies studies on biomarkers/indexes. Aim: To define blood cell count indexes and verify their association with pediatric CKD etiology and staging. The included indexes were: Neutrophil-Lymphocyte Ratio (NLR), Derived Neutrophil-Lymphocyte Ratio (dNLR), Lymphocyte-Monocyte Ratio (LMR), Systemic Inflammation Response Index (SIRI), Aggregate Index of Systemic Inflammation (AISI), and Systemic Immune-Inflammation Index (SII). Methods: We determined the indexes in 52 pediatric CKD patients and 33 healthy controls by mathematical calculation. CKD patients were separated in five groups based on the etiology and staging: Group IA: glomerulopathies at stage 1 or 2; IB: glomerulopathies at stage 3 or 4; IIA: CAKUT at stage 1 or 2; IIB: CAKUT at stage 3 or 4; and III: stages 3 or 4 of other etiologies. In addition, we combined all patients with CKD in one group (IV). Group V was a healthy control group. Results: Lower values of LMR were observed for groups IB and IIB compared to group V (p = 0.047, p = 0.031, respectively). Increased values of SIRI were found for group III versus group V (p = 0.030). There was no difference for other indexes when the groups were compared two by two. Conclusion: The LMR and SIRI indexes showed promising results in the evaluation of inflammation, as they correlated with CKD etiologies and specially staging in these patients.

Resumo Introdução: Doença renal crônica (DRC) é definida como um declínio progressivo das funções renais. Na infância, os principais fatores desencadeantes são anomalias congênitas dos rins e trato urinário (CAKUT) e glomerulopatias. Respostas inflamatórias apresentam desafios para diagnóstico e estadiamento, o que justifica estudos sobre biomarcadores/índices. Objetivo: Definir índices de contagem de células sanguíneas e verificar sua associação com etiologia e estadiamento da DRC pediátrica. Os índices incluídos foram: Razão Neutrófilo-Linfócito (NLR), Razão Neutrófilo-Linfócito Derivada (dNLR), Razão Linfócito-Monócito (LMR), Índice de Resposta à Inflamação Sistêmica (SIRI), Índice Agregado de Inflamação Sistêmica (AISI) e Índice de Inflamação Imune Sistêmica (SII). Métodos: Determinamos índices em 52 pacientes pediátricos com DRC e 33 controles saudáveis por cálculo matemático. Pacientes com DRC foram separados em cinco grupos conforme etiologia e estadiamento: Grupo IA: glomerulopatias em estágio 1 ou 2; IB: glomerulopatias em estágio 3 ou 4; IIA: CAKUT em estágio 1 ou 2; IIB: CAKUT em estágio 3 ou 4; e III: estágios 3 ou 4 de outras etiologias. Além disso, combinamos todos os pacientes com DRC em um grupo (IV). Grupo V foi um grupo controle saudável. Resultados: Observamos valores menores de LMR nos grupos IB e IIB comparados ao grupo V (p=0,047; p=0,031, respectivamente). Encontramos valores maiores de SIRI para o grupo III versus grupo V (p=0,030). Não houve diferença para outros índices quando os grupos foram comparados dois a dois. Conclusão: Os índices LMR e SIRI apresentaram resultados promissores na avaliação da inflamação, pois correlacionaram-se com as etiologias da DRC e, principalmente, com o estadiamento desses pacientes.

Application of Nanoparticles in Cancer Treatment: A Concise Review.

Timely diagnosis and appropriate antitumoral treatments remain of utmost importance, since cancer remains a leading cause of death worldwide. Within this context, nanotechnology offers specific benefits in terms of cancer therapy by reducing its adverse effects and guiding drugs to selectively target cancer cells. In this comprehensive review, we have summarized the most relevant novel outcomes in the range of 2010-2023, covering the design and application of nanosystems for cancer therapy. We have established the general requirements for nanoparticles to be used in drug delivery and strategies for their uptake in tumor microenvironment and vasculature, including the reticuloendothelial system uptake and surface functionalization with protein corona. After a brief review of the classes of nanovectors, we have covered different classes of nanoparticles used in cancer therapies. First, the advances in the encapsulation of drugs (such as paclitaxel and fisetin) into nanoliposomes and nanoemulsions are described, as well as their relevance in current clinical trials. Then, polymeric nanoparticles are presented, namely the ones comprising poly lactic-co-glycolic acid, polyethylene glycol (and PEG dilemma) and dendrimers. The relevance of quantum dots in bioimaging is also covered, namely the systems with zinc sulfide and indium phosphide. Afterwards, we have reviewed gold nanoparticles (spheres and anisotropic) and their application in plasmon-induced photothermal therapy. The clinical relevance of iron oxide nanoparticles, such as magnetite and maghemite, has been analyzed in different fields, namely for magnetic resonance imaging, immunotherapy, hyperthermia, and drug delivery. Lastly, we have covered the recent advances in the systems using carbon nanomaterials, namely graphene oxide, carbon nanotubes, fullerenes, and carbon dots. Finally, we have compared the strategies of passive and active targeting of nanoparticles and their relevance in cancer theranostics. This review aims to be a (nano)mark on the ongoing journey towards realizing the remarkable potential of different nanoparticles in the realm of cancer therapeutics.

Adenosinergic System and BDNF Signaling Changes as a Cross-Sectional Feature of RTT: Characterization of Mecp2 Heterozygous Mouse Females.

Rett Syndrome is an X-linked neurodevelopmental disorder (RTT; OMIM#312750) associated to MECP2 mutations. MeCP2 dysfunction is seen as one cause for the deficiencies found in brain-derived neurotrophic factor (BDNF) signaling, since BDNF is one of the genes under MeCP2 jurisdiction. BDNF signaling is also dependent on the proper function of the adenosinergic system. Indeed, both BDNF signaling and the adenosinergic system are altered in Mecp2-null mice (Mecp2-/y), a representative model of severe manifestation of RTT. Considering that symptoms severity largely differs among RTT patients, we set out to investigate the BDNF and ADO signaling modifications in Mecp2 heterozygous female mice (Mecp2+/-) presenting a less severe phenotype. Symptomatic Mecp2+/- mice have lower BDNF levels in the cortex and hippocampus. This is accompanied by a loss of BDNF-induced facilitation of hippocampal long-term potentiation (LTP), which could be restored upon selective activation of adenosine A2A receptors (A2AR). While no differences were observed in the amount of adenosine in the cortex and hippocampus of Mecp2+/- mice compared with healthy littermates, the density of the A1R and A2AR subtype receptors was, respectively, upregulated and downregulated in the hippocampus. Data suggest that significant changes in BDNF and adenosine signaling pathways are present in an RTT model with a milder disease phenotype: Mecp2+/- female animals. These features strengthen the theory that boosting adenosinergic activity may be a valid therapeutic strategy for RTT patients, regardless of their genetic penetrance.

Assessment of the in Vitro Antimelanoma Potential of Lippia microphylla Cham (Verbenaceae) Essential Oil.

Essential oils stand out among natural products for their complex composition, frequently described in the literature with a range of biological effects. This study evaluated the cytotoxic activity against several human cancer cell lines of essential oils extracted from the leaves of Lippia microphylla (EO-LM) Cham. (Verbenaceae). The melanoma cell line SK-MEL-28 was the most sensitive to the EO-LM, presenting an IC50 of 33.38±1.16 µg/mL. Afterward, the effects of EO-LM on the cell cycle, induction of apoptosis, and production of reactive oxygen species (ROS) were evaluated. We stated a significant increase in the sub-G1 population, indicating apoptosis, later confirmed by an increase of SK-MEL-28 cells labeled with Annexin V-FITC and by the formation of apoptotic bodies and membrane blebs, observed by confocal microscopy. Additionally, EO-LM reduced the production of ROS, indicating antioxidant activity. Therefore, EO-LM exhibits anti-melanoma activity in vitro, suggesting its potential as an anticancer agent.

Estudo sobre a prevalência de doença carotídea detectada por ultrassonografia nos casos de AVC isquêmico de um hospital público de Santa Catarina / Study on the prevalence of carotid artery disease detected by ultrasonography in cases of ischemic stroke at a public hospital in Santa Catarina

Fundamento: Acidentes Vasculares Cerebrais Isquêmicos (AVCi) representam significativa parcela dentre as causas da morbimortalidade mundial. Estenose das artérias carótidas e vertebrais são consideradas fator de risco para tal desfecho. A Ultrassonografia com Doppler (USG Doppler) das artérias extracranianas pode ser útil na identificação de pacientes com estenose significativa por ser um método inócuo e acessível. Objetivos: avaliar a prevalência de estenose nas artérias extracranianas diagnosticadas através do estudo com USG Doppler e a prevalência de fatores associados em pacientes com quadro de AVCi. Métodos: Trata-se de estudo retrospectivo, transversal, a partir da análise de prontuários dos pacientes internados com quadro de AVCi no Hospital Regional de São José, Santa Catarina, Brasil. O estudo ocorreu entre janeiro de 2020 e dezembro de 2021. A análise ultrassonográfica foi realizada por médicos radiologistas habilitados, a partir do uso de aparelho validado (GE Logic P9 com transdutor linear multifrequencial 6-15MHz). Resultados: Dentre os 239 pacientes incluídos, destaca-se a significativa prevalência de comorbidades associadas ao AVCi, como hipertensão arterial sistêmica (78,2%) e tabagismo (40,6%). A distribuição entre os sexos foi homogênea (58,2 versus 41,8%) e 70,3% dos pacientes possuíam idade superior a 60 anos de idade. A taxa de pacientes com alterações hemodinamicamente significativas (estenose >50% da luz do vaso) das artérias carótidas e vertebrais foi de 29,2%. O tabagismo foi o único fator de risco que se correlacionou estatisticamente com a ocorrência de AVCi decorrente do acometimento das artérias carótidas ou vertebrais (RP 1,708; IC 1,057-2,761; p=0,028). Conclusão: O USG com Doppler das artérias extracranianas é ferramenta útil na investigação dos casos de AVCi, visto que a prevalência de doença significativa dos grandes vasos extracranianos (estenose>50%) se aproxima de 30%.

Background: Ischemic Strokes represent a sizable portion among the causes of morbidity and mortality worldwide. Stenosis of the carotid and vertebral arteries represent a risk factor to this outcome. Ultrasonography with Doppler of the extracranial arteries can be useful in identifying patients with significant stenosis because it is a harmless and accessible method. Objectives: To assess the prevalence of stenosis in the extracranial arteries diagnosed through Doppler ultrasound examination and the prevalence of associated factors in patients with ischemic stroke Methods: This is a retrospective, cross-sectional study based on the analysis of medical records of patients admitted with ischemic stroke at the Regional Hospital of São José, Santa Catarina, Brazil. The study was conducted between January 2020 and December 2021. Ultrasonographic analysis was performed by qualified radiologists, using a validated device (GE Logic P9 with a multi-frequency linear transducer 6-15MHz). Results: Among the 239 included patients, there is a significant prevalence of comorbidities associated with ischemic stroke, such as systemic arterial hypertension (78.2%) and smoking (40.6%). The distribution between genders was homogeneous (58.2% versus 41.8%), and 70.3% of the patients were over 60 years old. The rate of patients with hemodynamically significant alterations (stenosis >50% of the vessel lumen) in the carotid and vertebral arteries was 29.2%. Smoking was the only risk factor that statistically correlated with the occurrence of ischemic stroke resulting from the involvement of the carotid or vertebral arteries (PR 1.708; CI 1.057-2.761; p=0.028). Conclusion: Ultrasonography with Doppler of the extracranial arteries is a useful tool in the investigation of ischemic stroke cases, given that the prevalence of significant disease in the large extracranial vessels (stenosis >50%) approaches 30%.

Surgical resection of retrohepatic inferior vena cava leiomyosarcoma without vascular reconstruction: case report.

Inferior vena cava leiomyosarcoma (IVCL) is a rare malignant mesenchymal tumor. Surgical treatment is a challenge because it must combine free surgical margins with vascular reconstruction, using prosthetic or autologous grafts, primary suture, or simple ligation without vein reconstruction. The ligation option is possible thanks to the slow growth of the tumor, allowing collateral venous circulation to develop. We present a case of an IVCL treated with radical resection without vascular reconstruction. The patient was a 48-year-old female with abdominal pain in the right upper quadrant, asthenia, and postprandial dyspeptic symptoms. Abdominal tomography revealed a mass with an expansive formation located in the infrahepatic segment of the inferior vena cava and reduced vessel lumen. During surgery, vein clamping did not provoke hemodynamic repercussions, suggesting sufficient collateral circulation formation. It was decided to perform a radical resection of the entire portion of the retrohepatic vena cava and ligate the vena cava without vascular reconstruction. The patient recovered without complications.

Severe infections in Portuguese patients with rheumatoid arthritis under biologic treatment - a multicenter, nationwide study (SIPPRA-B Study).

INTRODUCTION: Despite years of experience with biological disease modifying anti-rheumatic drugs (bDMARD) in rheumatoid arthritis (RA), little is known about differences in infectious risk among bDMARDs. The aim of this study was to assess the incidence and type of infections in RA patients on bDMARDs and to determine possible predictors. METHODS: A retrospective multicenter cohort study that included patients registered in the Rheumatic Diseases Portuguese Registry (Reuma.pt) with RA, and exposed to at least one bDMARD until April 2021. RA patients under bDMARD and with at least one episode of severe infection (SI), defined as infection that requires hospitalization, use of parenteral antibiotics or that resulted in death, were compared to patients with no report of SI. Demographic and clinical data at baseline and at the time of each SI were collected to establish comparisons between different groups of bDMARDs. Comparisons between different bDMARDs were assessed and logistic regression was performed to identify predictors of SI. RESULTS: We included 3394 patients, 2833 (83.5%) female, with a mean age at RA diagnosis of 45.5±13.7 years. SI was diagnosed in 142 of the 3394 patients evaluated (4.2%), totaling 151 episodes of SI. At baseline, patients with SI had a significantly higher proportion of prior orthopedic surgery, asthma, interstitial lung disease, chronic kidney disease and corticosteroid use, higher mean age and longer median disease duration at first bDMARD. Nine patients died (6.0%). Ninety-two SI (60.9%) occurred with the first bDMARD, the majority leading to discontinuation of the bDMARD within 6 months (n=75, 49.7%), while 65 (43.0%) restarted the same bDMARD and 11 (7.3%) switched to another bDMARD (6 of them to a different mechanism of action). In the multivariate analysis, we found that chronic kidney disease, asthma, infliximab, corticosteroid use, interstitial lung disease, previous orthopedic surgery, higher Health Assessment Questionnaire and DAS284V-ESR are independent predictors of SI. CONCLUSION: This study described the incidence and types of SI among Portuguese RA patients on biologics, identifying several predictors of SI, both globally and with different bDMARDs. Physicians should be aware of the real-word infectious risk in RA patients on bDMARDs when making treatment decisions.

Does patient and public involvement impact public health decision-making? A 10 year retrospective analysis of public consultation in Brazil.

BACKGROUND:  The aim of this work is to characterize the processes associated with patient and public involvement (PPI) in the form of public consultations (PC) during the first 10 years of operation of the National Committee for Health Technology Incorporation in the Unified Health System (Conitec) of Brazil, and to identify factors associated with changes in Conitec's recommendations following these PC. METHODS:  This cross-sectional study analysed all processes related to the adoption of technologies that took place in Brazil between 2012 and 2021 based on technical reports and self-reported information collected from PC participants. A multiple logistic regression model identified factors associated with changes in Conitec's recommendations following PC. RESULTS:  A total of 479 technical reports were published, of which 83% (n = 400) were submitted to PC. Demands were made mainly by applicants from the government (n = 262; 55%), regarding the adoption of medicines (n = 366; 76%), in which context neoplasms and infectious diseases were the most frequent indications (n = 66; 14% for each). A total of 264 (55%) processes resulted in a final recommendation in favour of introducing the technology. Over the period of 10 years, 196 483 contributions were received in response to PC. The largest volume of contributions was made by patients and their families or representatives (n = 99 082; 50%), females (122 895; 67%), white individuals (129 165; 71%) and individuals between the ages of 25 and 59 years (145 364; 80%). Alteration of the preliminary recommendation occurred in 13% (n = 53) of the PC, with a higher proportion of recommendations being altered from 2017 onwards. Increased participation by patients had a significant impact on the alteration of the preliminary recommendation (odds ratio 3.87, 95% CI 1.33-13.35, p = 0.02). CONCLUSIONS: Increased engagement of patients and their families and caregivers in PC was associated with changing the preliminary recommendation of Conitec about the adoption of technologies into the public health system in Brazil.

Sacral neuromodulation for low anterior resection syndrome: current status-a systematic review and meta-analysis.

INTRODUCTION: It is estimated that approximately 70% of patients with rectal cancer who undergo surgery will suffer from Low Anterior Resection Syndrome (LARS). In the last decades, sacral neuromodulation (SNM) has been widely used in urinary dysfunction and in faecal incontinence refractory to medical treatment. Its application in LARS has been investigated and has shown promising results. The paper's aim is to present a systematic review and meta-analysis of the available literature and evaluate the therapeutic success of SNM in patients with LARS. METHODS: A systematic search was performed in international health-related databases: Cochrane Library, EMBASE, PubMed and SciELO. No restrictions on year of publication or language were applied. Retrieved articles were screened and selected according to set inclusion criteria. Data items were collected and processed for each included article and a meta-analysis was done according to the PRISMA guidelines. The primary outcome was the number of successful definitive SNM implants. Further outcomes included changes in bowel habits, incontinence scores, quality of life scores, anorectal manometry data and complications. RESULTS: A total of 18 studies were included, with 164 patients being submitted to percutaneous nerve evaluation (PNE) with 91% responding successfully. During follow-up of therapeutic SNM some devices were explanted. The final clinical success rate was 77% after permanent implant. Other outcomes, such as the frequency of incontinent episodes, faecal incontinence scores, quality of life scores were overall improved after SNM. The meta-analysis showed a decrease in 10.11 incontinent episodes/week; a decrease of 9.86 points in the Wexner score and an increase in quality of life of 1.56 (pooled estimate). Changes in anorectal manometry were inconsistent. Local infection was the most common post-operative complication, followed by pain, mechanical issues, loss of efficacy and haematoma. DISCUSSION/CONCLUSION: This is the largest systematic review and meta-analysis concerning the use of SNM in LARS patients. The findings support the available evidence that sacral neuromodulation can be effective in the treatment of LARS, with significant improvement in total incontinent episodes and patients´ quality of life.

Primary Splenic Diffuse Large B-Cell Lymphoma: A Case Report.

Primary splenic lymphoma (PSL) is a rare disease and an improbable cause of splenomegaly or splenic nodules. On the contrary, splenic secondary involvement as part of an advanced lymphoproliferative disorder is more common. The authors present the case of a 49-year-old woman with a primary splenic diffuse large B-cell lymphoma (PS-DLBCL), in which the absence of other organs' involvement determined an ultrasound-guided biopsy of the spleen to achieve a definitive diagnosis. With this case the authors intend to emphasise the extensive differential diagnosis of splenomegaly, splenic nodules or infiltrates, the usefulness of splenic biopsy in establishing the diagnosis and recall a rare disease, with non-specific presenting symptoms, in which the diagnostic workup is challenging. LEARNING POINTS: The differential diagnosis of splenic nodules or infiltrates is vast and challenging, and it includes haematological diseases, systemic infectious diseases but also non-malignant infiltrative diseases.Although some lymphomas frequently present with splenomegaly, this is not the case of DLBCL, with the exception of PS-DLBCL.PS-DLBCL is a very rare pathology, accounting for 1% of all DLBCL and less than 1% of all NHL.