Efficacy and safety of once-weekly subcutaneous semaglutide in adults with overweight or obesity: systematic review with meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of once-weekly subcutaneous semaglutide treatment in overweight or obese patients without type 2 diabetes. METHODS: Randomized clinical trials that accessed the impact of once-weekly semaglutide on body weight and safety outcomes in overweight or obese patients were retrieved from Pubmed, EMBASE, and Lilacs up to November 2023. Risk of bias was assessed with RoB 2.0, and certainty of evidence (CoE) with GRADE. We conducted a random-effects meta-analysis. RESULTS: We included ten publications with 22.155 patients. Semaglutide decreased relative body weight (MD: -11.80; 95%CI: -13.53 to -10.07; CoE: High), absolute body weight (MD: -11.58; 95%CI: -13.25 to -9.90; CoE: High) and BMI (MD: -4.15; 95%CI: -4.85 to -3.45; CoE: High). Semaglutide also increased the proportion of patients who achieved 5%, 10% and 15% of weight loss ([weight loss ≥5%: RR 2.29, 95% CI: 1.88 to 2.80; CoE: High]; [weight loss ≥10%: RR 4.54, 95% CI: 3.45 to 5.98; CoE: High]; [weight loss ≥15%: RR 8.29, 95%CI: 5.54 to 12.39; CoE: High]). Semaglutide leads to small risk to adverse events (RR: 1.03; 95%CI: 1 to 1.06; CoE: High), no difference in the serious adverse events (RR: 1.07; 95%CI: 0.70 - 1.62; CoE: Low), but increases in the risk to discontinued treatment (RR: 2.03; 95%CI: 1.87 - 2.20; CoE: High) and gastrointestinal adverse events (RR: 3.26; 95%CI: 1.99 - 5.34; CoE: Moderate). CONCLUSION: This up-to-date systematic review highlights that once-weekly semaglutide treatment resulted in clinically important weight loss, becoming a promising adjuvant therapy to treat obesity.

Sodium-glucose cotransporter 2 inhibitors influence skeletal muscle pathology in patients with heart failure and reduced ejection fraction.

AIMS: Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms and decreased quality of life. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism of action remains poorly understood. We aimed, therefore, to determine whether SGLT2i influence skeletal muscle pathology in patients with HFrEF. METHODS AND RESULTS: Muscle biopsies from 28 male patients with HFrEF (New York Heart association class I-III) treated with SGLT2i (>12 months) or without SGLT2i were compared. Comprehensive analyses of muscle structure (immunohistochemistry), transcriptome (RNA sequencing), and metabolome (liquid chromatography-mass spectrometry) were performed, and serum inflammatory profiling (ELISA). Experiments in mice (n = 16) treated with SGLT2i were also performed. Myofiber atrophy was ~20% less in patients taking SGLT2i (p = 0.07). Transcriptomics and follow-up measures identified a unique signature in patients taking SGLT2i related to beneficial effects on atrophy, metabolism, and inflammation. Metabolomics identified influenced tryptophan metabolism in patients taking SGLT2i: kynurenic acid was 24% higher and kynurenine was 32% lower (p < 0.001). Serum profiling identified that SGLT2i treatment was associated with lower (p < 0.05) pro-inflammatory cytokines by 26-64% alongside downstream muscle interleukin (IL)-6-JAK/STAT3 signalling (p = 008 and 0.09). Serum IL-6 and muscle kynurenine were correlated (R = 0.65; p < 0.05). Muscle pathology was lower in mice treated with SGLT2i indicative of a conserved mammalian response to treatment. CONCLUSIONS: Treatment with SGLT2i influenced skeletal muscle pathology in patients with HFrEF and was associated with anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be regulated via IL-6-kynurenine signalling. Together, clinical improvements following SGLT2i treatment in patients with HFrEF may be partly explained by their positive effects on skeletal muscle pathology.

Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major clinical problem, with limited treatments. HFpEF is characterized by a distinct, but poorly understood, skeletal muscle pathology, which could offer an alternative therapeutic target. In a rat model, we identified impaired myonuclear accretion as a mechanism for low myofiber growth in HFpEF following resistance exercise. Acute caloric restriction rescued skeletal muscle pathology in HFpEF, whereas cardiac therapies had no effect. Mechanisms regulating myonuclear accretion were dysregulated in patients with HFpEF. Overall, these findings may have widespread implications in HFpEF, indicating combined dietary with exercise interventions as a beneficial approach to overcome skeletal muscle pathology.

Gait kinematics of osteoarthritic knees after intra-articular viscosupplementation: A double-blinded randomized controlled trial.

BACKGROUND: The utilization of subjective questionnaires for assessing conservative treatment in knee osteoarthritis may present challenges in identifying differences due to inadequate statistical power. Objective tools, such as three-dimensional (3D) kinematic analysis, are accurate and reproducible methods. However, no high-quality studies assessing the effects of intra-articular viscosupplementation (VS) have been published. Therefore, the objective of the study was to evaluate gait kinematics of patients with advanced knee osteoarthritis after VS. METHODS: Forty-two patients were randomized to receive either VS or saline injection (placebo). They underwent 3D kinematic gait analysis before and at 1, 6, and 12 weeks after treatment and knee angles during stance phase were determined. Patients and the healthcare team responsible for data collection, processing, and analysis were blinded to group allocation. Between-group comparisons were conducted using linear mixed models. RESULTS: Compared with placebo, the VS increased the maximum knee extension (3.2° (0.7-5.7)) and decreased the maximum knee flexion (-3.6° (-6.1 to -1.2)) on the sagittal plane at 1 week. At 6 weeks, the VS group sustained a reduced maximum knee flexion (-2.6° (-5.2 to 0.0)). On the axial plane, the VS group demonstrated an increase in maximum internal rotation at 12 weeks (3.9° (0.3 to 7.7)). The VS group exhibited reduced single-leg stance time at 1 week and increased total stance time at 12 weeks. CONCLUSIONS: VS led to short- and long-term kinematic improvements in the sagittal and axial planes, leading to a gait pattern closer to that observed in individuals with less severe osteoarthritic knees.

Examining O[Formula: see text] adsorption on pristine and defective popgraphene sheets: A DFT study.

CONTEXT: Popgraphene (PopG) is a two-dimensional carbon-based material with fused pentagonal and octagonal rings. Like graphene, it exhibits a metallic band gap and exceptional thermal, dynamic, and mechanical stability. Here, we theoretically study the electronic and structural properties of PopG monolayers, including their doped and vacancy-endowed versions, as O[Formula: see text] adsorbers. Our findings show that pristine and vacancy-endowed PopG sheets have a comparable ability to adsorb O[Formula: see text] molecules, with adsorption energies ranging from [Formula: see text]0.57 to [Formula: see text]0.59 eV (physisorption). In these cases, octagonal rings play a dominant role in the adsorption mechanism. Platinum and Silicon doping enhance the O[Formula: see text] adsorption in areas close to the octagonal rings, resulting in adsorption energies ranging from [Formula: see text]1.13 to [Formula: see text]2.56 eV (chemisorption). Furthermore, we computed the recovery time for the adsorbed O[Formula: see text] molecules. The results suggest that PopG/O[Formula: see text] interaction in pristine and vacancy-endowed cases can change the PopG electronic properties before O[Formula: see text] diffusion. METHODS: Density Functional Theory (DFT) simulations, with Van der Waals corrections (DFT-D, within the Grimme scheme), were performed to study the structural and electronic properties of PopG/O[Formula: see text] systems using the DMol3 code within the Biovia Materials Studio software. The exchange and correlation functions are treated within the generalized gradient approximation (GGA) as parameterized by Perdew-Burke-Ernzerhof (PBE) functional. We used the double-zeta plus polarization (DZP) for the basis set in these cases. We also considered the BSSE correction through the counterpoise method and the nuclei-valence electron interactions by including semi-core DFT pseudopotentials.

Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.

BACKGROUND: Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) share phenotypic and molecular commonalities, including the fact that they can be caused by mutations in ubiquitous proteins involved in RNA metabolism, namely SMN, TDP-43 and FUS. Although this suggests the existence of common disease mechanisms, there is currently no model to explain the resulting motor neuron dysfunction. In this work we generated a parallel set of Drosophila models for adult-onset RNAi and tagged neuronal expression of the fly orthologues of the three human proteins, named Smn, TBPH and Caz, respectively. We profiled nuclear and cytoplasmic bound mRNAs using a RIP-seq approach and characterized the transcriptome of the RNAi models by RNA-seq. To unravel the mechanisms underlying the common functional impact of these proteins on neuronal cells, we devised a computational approach based on the construction of a tissue-specific library of protein functional modules, selected by an overall impact score measuring the estimated extent of perturbation caused by each gene knockdown. RESULTS: Transcriptome analysis revealed that the three proteins do not bind to the same RNA molecules and that only a limited set of functionally unrelated transcripts is commonly affected by their knock-down. However, through our integrative approach we were able to identify a concerted effect on protein functional modules, albeit acting through distinct targets. Most strikingly, functional annotation revealed that these modules are involved in critical cellular pathways for motor neurons, including neuromuscular junction function. Furthermore, selected modules were found to be significantly enriched in orthologues of human neuronal disease genes. CONCLUSIONS: The results presented here show that SMA and ALS disease-associated genes linked to RNA metabolism functionally converge on neuronal protein complexes, providing a new hypothesis to explain the common motor neuron phenotype. The functional modules identified represent promising biomarkers and therapeutic targets, namely given their alteration in asymptomatic settings.

What If Root Nodules Are a Guesthouse for a Microbiome? The Case Study of Acacia longifolia.

Acacia longifolia is one of the most aggressive invaders worldwide whose invasion is potentiated after a fire, a common perturbation in Mediterranean climates. As a legume, this species establishes symbioses with nitrogen-fixing bacteria inside root nodules; however, the overall microbial diversity is still unclear. In this study, we addressed root nodules' structure and biodiversity through histology and Next-Generation Sequencing, targeting 16S and 25S-28S rDNA genes for bacteria and fungi, respectively. We wanted to evaluate the effect of fire in root nodules from 1-year-old saplings, by comparing unburnt and burnt sites. We found that although having the same general structure, after a fire event, nodules had a higher number of infected cells and greater starch accumulation. Starch accumulated in uninfected cells can be a possible carbon source for the microbiota. Regarding diversity, Bradyrhizobium was dominant in both sites (ca. 77%), suggesting it is the preferential partner, followed by Tardiphaga (ca. 9%), a non-rhizobial Alphaproteobacteria, and Synechococcus, a cyanobacteria (ca. 5%). However, at the burnt site, additional N-fixing bacteria were included in the top 10 genera, highlighting the importance of this process. Major differences were found in the mycobiome, which was diverse in both sites and included genera mostly described as plant endophytes. Coniochaeta was dominant in nodules from the burnt site (69%), suggesting its role as a facilitator of symbiotic associations. We highlight the presence of a large bacterial and fungal community in nodules, suggesting nodulation is not restricted to nitrogen fixation. Thus, this microbiome can be involved in facilitating A. longifolia invasive success.

Effect of the Administration of a Lyophilised Faecal Capsules on the Intestinal Microbiome of Dogs: A Pilot Study.

Faecal Microbiota Transplantation (FMT) is a promising strategy for modulating the gut microbiome. We aimed to assess the effect of the oral administration of capsules containing lyophilised faeces on dogs with diarrhoea for 2 months as well as evaluate their long-term influence on animals' faecal consistency and intestinal microbiome. This pilot study included five dogs: two used as controls and three with diarrhoea. Animals were evaluated for four months by performing a monthly faecal samples collection and physical examination, which included faecal consistency determination using the Bristol scale. The total number of viable bacteria present in the capsules was quantified and their bacterial composition was determined by 16S rRNA gene sequencing, which was also applied to the faecal samples. During the assay, no side effects were reported. Animals' faecal consistency improved and, after ending capsules administration, Bristol scale values remained stable in two of the three animals. The animals' microbiome gradually changed toward a composition associated with a balanced microbiota. After FMT, a slight shift was observed in its composition, but the capsules' influence remained evident during the 4-month period. Capsules administration seems to have a positive effect on the microbiota modulation; however, studies with more animals should be performed to confirm our observations.

Respiratory muscle training with electronic devices in the postoperative period of hepatectomy: A randomized study.

BACKGROUND: Many studies have been developed with a focus on surgical techniques and drugs, but few that address the importance of rehabilitation in the pre and postoperative period, and the specific benefits for each surgical procedure or type of neoplasm, aiming to minimize respiratory complications in the postoperative period. AIM: To compare the strength of the respiratory muscles in the pre and postoperative periods of hepatectomy by laparotomy and to verify the incidence of postoperative pulmonary complications among the groups studied. METHODS: Prospective, randomized, clinical trial study that compared the inspiratory muscle training group (GTMI) with the control group (CG). After the collection of sociodemographic and clinical data, in both groups, preoperatively, on the first and fifth postoperative days, vital signs and pulmonary mechanics were evaluated and recorded. Albumin and bilirubin values were recorded for the albumin-bilirubin (ALBI) score. After randomization and allocation of participants, those in the CG underwent conventional physical therapy and those in the GTMI underwent conventional physical therapy plus inspiratory muscle, in both groups for five postoperative days. RESULTS: Of 76 subjects met eligibility criteria. The collection of 41 participants was completed: 20 in the CG and 21 in the GTMI. The most frequent diagnosis was 41.5% with liver metastasis, followed by 26.8% with hepatocellular carcinoma. As for respiratory complications in the GTMI, there was no incidence. In the CG, there were three respiratory complications. Patients in the CG classified as ALBI score 3 presented, statistically, a higher energy value compared to patients classified as ALBI score 1 and 2 (P = 0.0187). Respiratory variables, measured preoperatively and on the first postoperative day, had a significant drop in both groups from the preoperative to the first postoperative day (P ≤ 0.0001). When comparing the preoperative period and the fifth postoperative day between the GTMI and the CG, the maximal inspiratory pressure variable in the GTMI was statistically significant (P = 0.0131). CONCLUSION: All respiratory measures showed a reduction in the postoperative period. Respiratory muscle training using the Powerbreathe® device increased maximal inspiratory pressure and this may have contributed to a shorter hospital stay and better clinical outcome.

DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.

DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3'end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.

Skeletal muscle atrophy, regeneration, and dysfunction in heart failure: Impact of exercise training.

This review highlights some established and some more contemporary mechanisms responsible for heart failure (HF)-induced skeletal muscle wasting and weakness. We first describe the effects of HF on the relationship between protein synthesis and degradation rates, which determine muscle mass, the involvement of the satellite cells for continual muscle regeneration, and changes in myofiber calcium homeostasis linked to contractile dysfunction. We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment. Overall, HF causes multiple impairments related to autophagy, anabolic-catabolic signaling, satellite cell proliferation, and calcium homeostasis, which together promote fiber atrophy, contractile dysfunction, and impaired regeneration. Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF, the effects of satellite cell dynamics remain poorly explored.

A New Perspective for Vineyard Terroir Identity: Looking for Microbial Indicator Species by Long Read Nanopore Sequencing.

Grapevine is one of the most important fruit crops worldwide, being Portugal one of the top wine producers. It is well established that wine sensory characteristics from a particular region are defined by the physiological responses of the grapevine to its environment and thus, the concept of terroir in viticulture was established. Among all the factors that contribute to terroir definition, soil microorganisms play a major role from nutrient recycling to a drastic influence on plant fitness (growth and protection) and of course wine production. Soil microbiome from four different terroirs in Quinta dos Murças vineyard was analysed through long-read Oxford Nanopore sequencing. We have developed an analytical pipeline that allows the identification of function, ecologies, and indicator species based on long read sequencing data. The Douro vineyard was used as a case study, and we were able to establish microbiome signatures of each terroir.

Deletion of Glycogen Synthase Kinase 3 Beta Reprograms NK Cell Metabolism.

Loss of cytotoxicity and defective metabolism are linked to glycogen synthase kinase 3 beta (GSK3ß) overexpression in natural killer (NK) cells from patients with acute myeloid leukemia or from healthy donors after expansion ex vivo with IL-15. Drug inhibition of GSK3ß in these NK cells improves their maturation and cytotoxic activity, but the mechanisms of GSK3ß-mediated dysfunction have not been well studied. Here, we show that expansion of NK cells with feeder cells expressing membrane-bound IL-21 maintained normal GSK3ß levels, allowing us to study GSK3ß function using CRISPR gene editing. We deleted GSK3B and expanded paired-donor knockout and wild-type (WT) NK cells and then assessed transcriptional and functional alterations induced by loss of GSK3ß. Surprisingly, our data showed that deletion of GSK3B did not alter cytotoxicity, cytokine production, or maturation (as determined by CD57 expression). However, GSK3B-KO cells demonstrated significant changes in expression of genes related to rRNA processing, cell proliferation, and metabolic function, suggesting possible metabolic reprogramming. Next, we found that key genes downregulated in GSK3B-KO NK cells were upregulated in GSK3ß-overexpressing NK cells from AML patients, confirming this correlation in a clinical setting. Lastly, we measured cellular energetics and observed that GSK3B-KO NK cells exhibited 150% higher spare respiratory capacity, a marker of metabolic fitness. These findings suggest a role for GSK3ß in regulating NK cell metabolism.

Utility of outdoor central site monitoring in assessing exposure of school children to ultrafine particles.

Epidemiological studies investigating the association between daily particle exposure and health effects are frequently based on a single monitoring site located in an urban background. Using a central site in epidemiological time-series studies has been established based on the premises of low spatial variability of particles within the areas of interest and hence the adequacy of the central sites to monitor the exposure. This is true to a large extent in relation to larger particles (PM2.5, PM10) that are typically monitored and regulated. However, the distribution of ultrafine particles (UFP), which in cities predominantly originate from traffic, is heterogeneous. With increasing pressure to improve the epidemiology of UFP, an important question to ask is, whether central site monitoring is representative of community exposure to this size fraction of particulate matter; addressing this question is the aim of this paper. To achieve this aim, we measured personal exposure to UFP, expressed as particle number concentration (PNC), using Philips Aerasense Nanotracers (NT) carried by the participants of the study, and condensation particle counters (CPC) or scanning mobility particle sizers (SMPS) at central fixed-site monitoring stations. The measurements were conducted at three locations in Brisbane (Australia), Cassino (Italy) and Accra (Ghana). We then used paired t-tests to compare the average personal and average fixed-site PNC measured over the same 24-h, and hourly, periods. We found that, at all three locations, the 24-h average fixed-site PNC was no different to the personal PNC, when averaged over the study period and all the participants. However, the corresponding hourly averages were significantly different at certain times of the day. These were generally times spent commuting and during cooking and eating at home. Our analysis of the data obtained in Brisbane, showed that maximum personal exposure occurred in the home microenvironment during morning breakfast and evening dinner time. The main source of PNC for personal exposure was from the home-microenvironment. We conclude that the 24-h average PNC from the central-site can be used to estimate the 24-h average personal exposure for a community. However, the hourly average PNC from the central site cannot consistently be used to estimate hourly average personal exposure, mainly because they are affected by very different sources.

Formoterol reduces muscle wasting in mice undergoing doxorubicin chemotherapy.

Background: Even though doxorubicin (DOX) chemotherapy promotes intense muscle wasting, this drug is still widely used in clinical practice due to its remarkable efficiency in managing cancer. On the other hand, intense muscle loss during the oncological treatment is considered a bad prognosis for the disease's evolution and the patient's quality of life. In this sense, strategies that can counteract the muscle wasting induced by DOX are essential. In this study, we evaluated the effectiveness of formoterol (FOR), a ß2-adrenoceptor agonist, in managing muscle wasting caused by DOX. Methods and results: To evaluate the effect of FOR on DOX-induced muscle wasting, mice were treated with DOX (2.5 mg/kg b.w., i.p. administration, twice a week), associated or not to FOR treatment (1 mg/kg b.w., s.c. administration, daily). Control mice received vehicle solution. A combination of FOR treatment with DOX protected against the loss of body weight (p<0.05), muscle mass (p<0.001), and grip force (p<0.001) promoted by chemotherapy. FOR also attenuated muscle wasting (p<0.01) in tumor-bearing mice on chemotherapy. The potential mechanism by which FOR prevented further DOX-induced muscle wasting occurred by regulating Akt/FoxO3a signaling and gene expression of atrogenes in skeletal muscle. Conclusions: Collectively, our results suggest that FOR can be used as a pharmacological strategy for managing muscle wasting induced by DOX. This study provides new insights into the potential therapeutic use of FOR to improve the overall wellbeing of cancer patients undergoing DOX chemotherapy.

Virulence-related metabolism is activated in Botrytis cinerea mostly in the interaction with tolerant green grapes that remain largely unaffected in contrast with susceptible green grapes.

Botrytis cinerea is responsible for the gray mold disease, severely affecting Vitis vinifera grapevine and hundreds of other economically important crops. However, many mechanisms of this fruit-pathogen interaction remain unknown. The combined analysis of the transcriptome and metabolome of green fruits infected with B. cinerea from susceptible and tolerant genotypes was never performed in any fleshy fruit, mostly because green fruits are widely accepted to be resistant to this fungus. In this work, peppercorn-sized fruits were infected in the field or mock-treated, and berries were collected at green (EL32) stage from a susceptible (Trincadeira) and a tolerant (Syrah) variety. RNAseq and GC-MS data suggested that Syrah exhibited a pre-activated/basal defense relying on specific signaling pathways, hormonal regulation, namely jasmonate and ethylene metabolisms, and linked to phenylpropanoid metabolism. In addition, putative defensive metabolites such as shikimic, ursolic/ oleanolic, and trans-4-hydroxy cinnamic acids, and epigallocatechin were more abundant in Syrah than Trincadeira before infection. On the other hand, Trincadeira underwent relevant metabolic reprogramming upon infection but was unable to contain disease progression. RNA-seq analysis of the fungus in planta revealed an opposite scenario with higher gene expression activity within B. cinerea during infection of the tolerant cultivar and less activity in infected Trincadeira berries. The results suggested an activated virulence state during interaction with the tolerant cultivar without visible disease symptoms. Together, this study brings novel insights related to early infection strategies of B. cinerea and the green berry defense against necrotrophic fungi.

Estratégias de publicidade por áreas de atuação odontológica na rede social Instagram® / Advertising strategies by dental practice areas on the social network Instagram®

Introdução: O Instagram® é a quarta rede social mais popular em todo o mundo para criar e compartilhar conteúdos editáveis e a mais utilizada para buscar serviços de saúde. Considerando que as redes sociais estão cada vez mais interligadas com a Odontologia e o mercado de trabalho, o objetivo dessa pesquisa foi classificar as estratégias de publicidade utilizadas na rede social Instagram® pelos cirurgiões-dentistas nas áreas de atuação. Material e métodos: Trata-se de um estudo quantitativo, transversal e retrospectivo. Os dados foram prospectados a partir de hashtags relacionadas à Odontologia, em dois períodos diferentes (janeiro/2022) e (março/2022). As postagens foram identificadas por áreas odontológicas e as imagens e/ou legendas classificadas de acordo com a estratégia de publicidade utilizada e realizou-se uma análise descritiva. Resultados: Em relação à imagem, de 1.111 posts, 87,1% (n=965) utilizaram apenas uma estratégia de publicidade e 12,9% de duas a cinco estratégias na mesma postagem. Quanto à legenda, de 529 publicações, 48,4% (n=256) corresponderam a uma estratégia e 51,6% (n=273) de duas até quatro simultaneamente. As estratégias mais frequentes na imagem foram 'lembranças de serviços odontológicos' (29,5%) e 'antes e depois' (16,1%) e, na legenda 'explicativo' (40,1%) e 'lembranças de serviços odontológicos' (31,7%). Conclusão: Áreas que valorizam o resultado estético alcançado, como odontologia integrada, harmonização orofacial, dentística, periodontia, ortodontia e prótese exploram mais o 'antes e depois', enquanto que outras áreas relacionadas ao tratamento e prevenção de doenças estão mais relacionadas a 'lembranças de serviços odontológicos'

Introduction: Instagram® is the fourth most popular social network worldwide to create and share editable content and the most used to search for health services. Considering that social networks are increasingly intertwined with Dentistry and the job market, the objective of this research was to classify the advertising strategies used in the social network Instagram® by dentists in their areas of expertise. Material and method: This is a quantitative, cross-sectional and retrospective study. Data were prospected from hashtags related to Dentistry, in two different periods (January/2022) and (March/2022). The posts were identified by dental areas and the images and/or captions classified according to the advertising strategy used and a descriptive analysis was carried out. Results: Regarding the image, of 1,111 posts, 87.1% (n=965) used only one advertising strategy and 12.9% used two to five strategies in the same post. As for the caption, of 529 publications, 48.4% (n=256) corresponded to one strategy and 51.6% (n=273) from two to four simultaneously. The most frequent strategies in the image were 'souvenirs of dental services' (29.5%) and 'before and after' (16.1%) and, in the caption 'explanatory' (40.1%) and 'souvenirs of dental services ' (31.7%). Conclusion: Areas that value the aesthetic result achieved, such as integrated dentistry, orofacial harmonization, dentistry, periodontics, orthodontics and prosthesis explore more the 'before and after', while other areas related to the treatment and prevention of diseases are more related to 'memories of dental services'

Nisin Mutant Prevention Concentration and the Role of Subinhibitory Concentrations on Resistance Development by Diabetic Foot Staphylococci.

The most prevalent microorganism in diabetic foot infections (DFI) is Staphylococcus aureus, an important multidrug-resistant pathogen. The antimicrobial peptide nisin is a promising compound for DFI treatment, being effective against S. aureus. However, to avoid the selection of resistant mutants, correct drug therapeutic doses must be established, being also important to understand if nisin subinhibitory concentrations (subMIC) can potentiate resistant genes transfer between clinical isolates or mutations in genes associated with nisin resistance. The mutant selection window (MSW) of nisin was determined for 23 DFI S. aureus isolates; a protocol aiming to prompt vanA horizontal transfer between enterococci to clinical S. aureus was performed; and nisin subMIC effect on resistance evolution was assessed through whole-genome sequencing (WGS) applied to isolates subjected to a MEGA-plate assay. MSW ranged from 5-360 µg/mL for two isolates, from 5-540 µg/mL for three isolates, and from 5-720 µg/mL for one isolate. In the presence of nisin subMIC values, no transconjugants were obtained, indicating that nisin does not seem to promote vanA transfer. Finally, WGS analysis showed that incubation in the presence of nisin subMIC did not promote the occurrence of significant mutations in genes related to nisin resistance, supporting nisin application to DFI treatment.