Dual-functionalized architecture enables stable and tumor cell-specific SiO2NPs in complex biological fluids.

Most commercial anticancer nanomedicines are administered intravenously. This route is fast and precise as the drug enters directly into the systemic circulation, without undergoing absorption processes. When nanoparticles come into direct contact with the blood, however, they interact with physiological components that can induce colloidal destabilization and/or changes in their original biochemical identity, compromising their ability to selectively accumulate at target sites. In this way, these systems usually lack active targeting, offering limited therapeutic effectiveness. In the literature, there is a paucity of in-depth studies in complex environments to evaluate nanoparticle stability, protein corona formation, hemolytic activity, and targeting capabilities. To address this issue, fluorescent silica nanoparticles (SiO2NPs) are here functionalized with zwitterionic (kinetic stabilizer) and folate groups (targeting agent) to provide selective interaction with tumor cell lines in biological media. The stability of these dually functionalized SiO2NPs is preserved in unprocessed human plasma while yielding a decrease in the number of adsorbed proteins. Experiments in murine blood further proved that these nanoparticles are not hemolytic. Remarkably, the functionalized SiO2NPs are more internalized by tumor cells than their healthy counterparts. Investigations of this nature play a crucial role in garnering results with greater reliability, allowing the development of nanoparticle-based pharmaceutical drugs that exhibit heightened efficacy and reduced toxicity for medical purposes.

New Report of Cyanobacteria and Cyanotoxins in El Pañe Reservoir: A Threat for Water Quality in High-Andean Sources from PERU.

Cyanobacteria are cosmopolitan organisms; nonetheless, climate change and eutrophication are increasing the occurrence of cyanobacteria blooms (cyanoblooms), thereby raising the risk of cyanotoxins in water sources used for drinking, agriculture, and livestock. This study aimed to determine the presence of cyanobacteria, including toxigenic cyanobacteria and the occurrence of cyanotoxins in the El Pañe reservoir located in the high-Andean region, Arequipa, Peru, to support water quality management. The study included morphological observation of cyanobacteria, molecular determination of cyanobacteria (16S rRNA analysis), and analysis of cyanotoxins encoding genes (mcyA for microcystins, cyrJ for cylindrospermopsins, sxtl for saxitoxins, and AnaC for anatoxins). In parallel, chemical analysis using Liquid Chromatography coupled with Mass Spectrometry (LC-MS/MS) was performed to detect the presence of cyanotoxins (microcystins, cylindrospermopsin, saxitoxin, and anatoxin, among others) and quantification of Microcystin-LR. Morphological data show the presence of Dolichospermum sp., which was confirmed by molecular analysis. Microcystis sp. was also detected through 16S rRNA analysis and the presence of mcyA gene related to microcystin production was found in both cyanobacteria. Furthermore, microcystin-LR and demethylated microcystin-LR were identified by chemical analysis. The highest concentrations of microcystin-LR were 40.60 and 25.18 µg/L, in May and November 2022, respectively. Microcystins were detected in cyanobacteria biomass. In contrast, toxins in water (dissolved) were not detected. Microcystin concentrations exceeded many times the values established in Peruvian regulation and the World Health Organization (WHO) in water intended for human consumption (1 µg/L). This first comprehensive report integrates morphological, molecular, and chemical data and confirms the presence of two toxigenic cyanobacteria and the presence of microcystins in El Pañe reservoir. This work points out the need to implement continuous monitoring of cyanobacteria and cyanotoxins in the reservoir and effective water management measures to protect the human population from exposure to these contaminants.

Development and Biocompatibility Assessment of Decellularized Porcine Uterine Extracellular Matrix-Derived Grafts.

Biomaterials derived from biological matrices have been widely investigated due to their great therapeutic potential in regenerative medicine, since they are able to induce cell proliferation, tissue remodeling, and angiogenesis in situ. In this context, highly vascularized and proliferative tissues, such as the uterine wall, present an interesting source to produce acellular matrices that can be used as bioactive materials to induce tissue regeneration. Therefore, this study aimed to establish an optimized protocol to generate decellularized uterine scaffolds (dUT), characterizing their structural, compositional, and biomechanical properties. In addition, in vitro performance and in vivo biocompatibility were also evaluated to verify their potential applications for tissue repair. Results showed that the protocol was efficient to promote cell removal, and dUT general structure and extracellular matrix composition remained preserved compared with native tissue. In addition, the scaffolds were cytocompatible, allowing cell growth and survival. In terms of biocompatibility, the matrices did not induce any signs of immune rejection in vivo in a model of subcutaneous implantation in immunocompetent rats, demonstrating an indication of tissue integration after 30 days of implantation. In summary, these findings suggest that dUT scaffolds could be explored as a biomaterial for regenerative purposes, which is beyond the studies in the reproductive field.

Improved protocol for histological and histopathological preparation of large eyes.

The development of new treatments for ocular diseases often requires investigating eyes similar in size and structure to human eyes. Such studies are challenging because analyzing the histopathology of large, human-sized eyes can be technically difficult. In particular, obtaining high-quality frozen sections is almost impossible due to the formation of ice crystals in the vitreous, which causes crush artifacts during the procedures of section and post sectioning manipulations. Herein, we describe a new method that provides high-quality frozen sections for large eyes and demonstrate its usefulness in the eyes of rabbits, pigs, minipigs, monkeys, and humans. We observed that artifactual separation of the photoreceptors from the retinal pigment epithelium is minimized and photoreceptor morphology is preserved. This method can be highly beneficial for investigators seeking to translate new treatments for ocular disease into the clinic. RESEARCH HIGHLIGHTS: Histopathological analysis of large and human-sized eyes presents significant challenges, particularly in obtaining high-quality frozen sections. A multistep fixation followed by vitreous removal and replacement ensures better cryopreservation and embedding of large eyes, minimizing the morphological and structural retinal loss found in many studies. Our results demonstrate that a multistep fixation and cryopreservation method for large eyes in histopathology consistently minimizes the artifactual separation of photoreceptors from the retinal pigment epithelium, thereby preserving photoreceptor morphology and providing high-quality frozen sections. A new method providing high-quality sections is necessary and will be highly useful for investigators aiming to translate new treatments for ocular diseases into clinical applications.

A conversational agent for enhanced Self-Management after cardiothoracic surgery.

BACKGROUND: Enhanced self-management is crucial for long-term survival following cardiothoracic surgery. OBJECTIVES: This study aimed to develop a conversational agent to enhance patient self-management after cardiothoracic surgery. METHODOLOGY: The solution was designed and implemented following the Design Science Research Methodology. A pilot study was conducted at the hospital to assess the feasibility, usability, and perceived effectiveness of the solution. Feedback was gathered to inform further interactions. Additionally, a focus group with clinicians was conducted to evaluate the acceptability of the solution, integrating insights from the pilot study. RESULTS: The conversational agent, implemented using a rule-based model, was successfully tested with patients in the cardiothoracic surgery unit (n = 4). Patients received one month of text messages reinforcing clinical team recommendations on a healthy diet and regular physical activity. The system received a high usability score, and two patients suggested adding a feature to answer user prompts for future improvements. The focus group feedback indicated that while the solution met the initial requirements, further testing with a larger patient cohort is necessary to establish personalized profiles. Moreover, clinicians recommended that future iterations prioritize enhanced personalization and interoperability with other hospital platforms. Additionally, while the use of artificial generative intelligence was seen as relevant for content personalization, clinicians expressed concerns regarding content safety, highlighting the necessity for rigorous testing. CONCLUSIONS: This study marks a significant step towards enhancing post-cardiothoracic surgery care through conversational agents. The integration of a diversity of stakeholder knowledge enriches the solution, grants ownership and ensures its sustainability. Future research should focus on automating message generation and delivery based on patient data and environmental factors. While the integration of artificial generative intelligence holds promise for enhancing patient interaction, ensuring the safety of its content is essential.

Exploring the cyanobacterial diversity in Portugal: Description of four new genera from LEGE-CC using the polyphasic approach.

Culture collections such as the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) hold approximately 1200 cyanobacterial strains and are critical community resources. However, many isolates in this and other collections have not been described with a polyphasic approach, and this limits further study. Here, we employed a polyphasic methodology that integrates 16S rRNA gene phylogenetic analyses, similarity (p-distance), 16S-23S ITS rRNA region secondary structures, morphological analyses, and habitat assessments to describe four novel cyanobacterial genera from the LEGE-CC, Portugal. Pseudolimnococcus planktonicus gen. et sp. nov. (Chroococcales) is phylogenetically and morphologically related to Limnococcus. The 16S rRNA gene similarity between the types of both genera is only 93.1%. Morphologically, Pseudolimnococcus cells do not reach the original spherical shape before the next division or have aerotopes and firm mucilage, while Limnococcus cells reach the original shape, lack aerotopes, and have diffluent mucilage. Eucapsopsis lusitanus gen. et sp. nov. (Chroococcales) is morphologically similar to Eucapsis but differs from it by having aerotopes and diffluent envelope. Eucapsis lacks aerotopes and has firm mucilaginous envelopes, rarely diffluent. Both genera are phylogenetically very distant from each other and have only 90.68% 16S rRNA gene similarity. Pseudoacaryochloris arrabidensis gen. et sp. nov. (Acaryochloridales) differs from Acaryochloris by the lack of mucilaginous envelope, which is present in Acaryochloris. Both genera are phylogenetically distant and have only 94.1% 16S rRNA gene similarity. Moreover, Acaryochloris is marine (sponge symbiont), while Pseudoacaryochloris is from freshwater. Vasconcelosia minhoensis gen. et sp. nov. (Nodosilineales) is phylogenetically related to Cymatolege but has only 94.3% similarity with this genus. Morphologically both genera are distinct. Vasconcelosia has a Romeria-like structure, while Cymatolege has a Phormidium-like structure. In all cases the 16S-23S ITS rRNA region secondary structures are in agreement with the other analyses. These novel genera expand the diversity of cyanobacteria in culture collections.

Suture versus tacks in minimally invasive transabdominal preperitoneal inguinal repair: a meta-analysis of randomized controlled trials.

INTRODUCTION: There is uncertainty regarding the method of mesh fixation and peritoneal closure during transabdominal preperitoneal (TAPP) repair for inguinal hernias, with no definitive guidelines to guide surgeon choice. METHODS: MEDLINE, Cochrane, Central Register of Clinical Trials, and Web of Science were searched for RCTs published until November 2023. Risk ratios (RRs) and mean differences (MD) with 95% confidence intervals (CIs) were pooled with a random-effects model. Statistical significance was defined as p < 0.05. Heterogeneity was assessed using the Cochran Q test and I2 statistics, with p values inferior to 0.10 and I2 > 25% considered significant. Statistical analyses were conducted using Review Manager version 5.4 and RStudio version 4.1.2 (R Foundation for Statistical Computing). RESULTS: Eight randomized controlled trials (RCTs) were included, comprising 624 patients, of whom 309 (49.5%) patients were submitted to TAPP with the use of tacks, and 315 (50.5%) received suture fixation. The use of tacker fixation was associated with a significant increase in postoperative pain at 24 h (MD 0.79 [VAS score]; 95% CI 0.38 to 1.19; p < 0.0002; I2 = 87%) and one week (MD 0.42 [VAS score]; 95% CI 0.05 to 0.79; p < 0.03, I2 = 84%). The use of tacks was associated with shorter operative time (MD-25.80 [min]; 95% - 34.31- - 17.28; P < 0.00001; I2 = 94%). No significant differences were found in overall complications, chronic pain, seromas, hematomas, and urinary retention rates. CONCLUSION: In patients who underwent TAPP hernia repair, tacks are associated with decreased operative time but increased postoperative pain at 24 h and one week.

The Impacts of Climate Change on the Emergence and Reemergence of Mosquito-Borne Diseases in Temperate Zones: An Umbrella Review Protocol.

INTRODUCTION: Mosquito-borne diseases represent a global public health concern and are responsible for over 700 000 deaths globally every year. Additionally, many mosquito species have undergone a dramatic global expansion due to various factors, including climate change, and forecasts indicate that mosquito populations will persist in dispersing beyond their present geographic range, namely in temperate climates. The research literature on this topic has grown in recent years, including some systematic evidence synthesis. However, to provide a comprehensive overview of this growing literature needed for policy action, a summary of this evidence, including existing systematic reviews, is required. This study aims to undertake an umbrella review that explores the impacts of climate change on the emergence and reemergence of diseases transmitted by mosquitoes in temperate zones and the publication of the protocol is a fundamental step to ensure the credibility, transparency and reproducibility of this research. METHODS AND ANALYSIS: Studies published in scientific journals indexed by PubMed, EMBASE, Cochrane Library, Epistemonikos, and Web of Science Core Collection to be included in this umbrella review will meet the following criteria: the topic of study (climate change and mosquito-borne diseases), regions (temperate zones), study designs (systematic reviews and meta-analysis), language (any) and date (since inception until December 31st, 2023). Titles and abstracts from selected articles will be evaluated by two authors independently and any discrepancy will be resolved through consensus or, if not possible, through a third author. The data will be extracted, and the risk of bias will be evaluated. The quality of the methodology of the included reviews will be assessed using AMSTAR 2. A narrative synthesis will examine the included systematic reviews. The quality of evidence for all outcomes will be judged using the Grading of Recommendations Assessment, Development and Evaluation working group methodology.

Abatacept inhibits Th17 differentiation and mitigates α-synuclein-induced dopaminergic dysfunction in mice.

Parkinson's disease (PD) is a multifaceted disease characterized by degeneration of nigrostriatal dopaminergic neurons, which results in motor and non-motor dysfunctions. Accumulation of α-synuclein (αSYN) in Lewy bodies is a key pathological feature of PD. Although the exact cause of PD remains unknown, accumulating evidence suggests that brain infiltration of T cells plays a critical role in the pathogenesis of disease, contributing to neuroinflammation and dopaminergic neurodegeneration. Here, we used a mouse model of brain-infused aggregated αSYN, which recapitulates motor and non-motor dysfunctions seen in PD patients. We found that αSYN-induced motor dysfunction in mice is accompanied by an increased number of brain-residing Th17 (IL17+ CD4+) cells, but not CD8+ T cells. To evaluate whether the modulation of T cell response could rescue αSYN-induced damage, we chronically treated animals with abatacept (8 mg/kg, sc, 3x per week), a selective T-cell co-stimulation modulator. We found that abatacept treatment decreased Th1 (IFNƔ+ CD4+) and Th17 (IL17+ CD4+) cells in the brain, rescued motor function and prevented dopaminergic neuronal loss in αSYN-infused mice. These results highlight the significance of effector CD4+ T cells, especially Th17, in the progression of PD and introduce novel possibilities for repurposing immunomodulatory drugs used for arthritis as PD-modifying therapies.

Region-Specific Decellularization of Porcine Uterine Tube Extracellular Matrix: A New Approach for Reproductive Tissue-Engineering Applications.

The uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which is directly associated to its functions. Considering this, the application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. The decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed the ECM composition and structure by optical and scanning electronic microscopy, FTIR, and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting a significative reduction in cellular content. Structural and spectroscopy analyses revealed that the produced scaffolds remained well structured and with the ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing high cell viability rates and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

Inflammatory response to bioceramic and epoxy resin-based endodontic sealers implanted in mice subcutaneous tissue: An in vivo study.

To evaluate the inflammatory tissue response to BioRoot™ RCS (BR) and AH Plus Jet (AHPJ) sealers implanted in mice subcutaneous tissue. It was hypothesized that the inflammatory tissue response to BR would be milder than to AHPJ. An in vivo study was carried out using isogenic mice. The sealers were implanted during standardized surgical procedures. The inflammatory response was evaluated by microscopic analysis and von Kossa reaction in the reactionary tissue around the specimens after 7, 21, and 63 days. For comparisons, a zinc oxide and eugenol sealer (ZOE) was used as a positive control, in addition to a negative control without a sealer (n = 10 per group/period). All statistical analyses considered a significance level of 5%. All endodontic sealers triggered an inflammatory tissue response after 7 days. BR had a higher inflammatory cell count and a thicker fibrous capsule when compared with AHPJ, but both were less inflammatory than ZOE (p < .001). After 21 days, BR continued to trigger an intense inflammatory tissue response, higher in both microscopic parameters compared to AHPJ, and a thicker fibrous capsule than ZOE (p < .001). After 63 days, the inflammatory tissue response decreased in BR, matching the fibrous capsule thickness with AHPJ and ZOE. BR promoted intense calcium precipitation in all study periods. After 63 days, AHPJ and BR sealers were more biocompatible to subcutaneous mice tissue, but AHPJ present better early inflammatory response, as well as BR showed potential bioactivity. RESEARCH HIGHLIGHTS: The inflammatory tissue response triggered by a bioceramic endodontic sealer (BR) was not milder than that triggered by an epoxy-resin based endodontic sealer (AHPJ) during the first 3 weeks, considering the microscopic analysis of the reactionary tissue.

Outpatient dental procedures carried out by Pediatric Dentists within Brazil's public healthcare system.

Brazil's public healthcare system (SUS) offers specialized oral health services to Brazilians, but the productivity of specialists, such as Pediatric Dentists, has not been characterized. Therefore, the objective of this study was to characterize the outpatient dental procedures (ODPs) carried out by Pediatric Dentists within the SUS. An epidemiological study with an ecological, longitudinal, retrospective, and quantitative approach was conducted. The ODPs carried out by Pediatric Dentists within the SUS were characterized based on type of procedure, complexity level, and circumstance (urgent or elective). Data were analyzed using a descriptive and analytical approach, considering a significance level of 5%, as well as the impact of the COVID-19 pandemic (the 2020-2022 years were not included in secondary analyses). In the last 15 years, 29,234,972 ODPs were carried out by Pediatric Dentists within the SUS. Clinical procedures were the majority (55.4%), significantly more frequent than all other types of procedures (all p <0.05). Among these, restorative and periodontal procedures were the most common (30.7% and 21.0%, respectively). From 2008 to 2019, excluding COVID-19 pandemic years, the trend over the last 15 years was constant for all types of procedures (all p >0.05). In addition, low complexity ODPs were the majority (90.1%), significantly more frequent than medium (9.7%) and high complexity procedures (0.1%) (both p <0.05). At last, most ODPs were not characterized by circumstance in the outpatient production reports (96.9%). Therefore, it was possible to conclude that Pediatric Dentists carried out diverse ODPs within the SUS over the past 15 years, although there was a dominant pattern of type and complexity.

Dereplication of 4-Quinolone Alkaloids from Waltheria Indica (Malvaceae) Tissues Using Molecular Network Tools.

Waltheria indica (Malvaceae) is a plant popularly used in folk medicine by traditional African and indigenous communities, and in various countries worldwide, to treat general inflammation. Several biological activities of this plant have been reported, including acetylcholinesterase inhibition and potential anti-human immunodeficiency virus (HIV), antinociceptive, analgesic, antifungal, anticancer, anti-inflammatory, leishmanicidal, trypanocidal, antioxidant, and antibacterial activities. The chemical profile of Waltheria indica was assessed by dereplication analysis using UPLC-MS/MS, and data acquisition was performed using chemoinformatics tools, such as Mass Spectrometry-Data Independent AnaLysis (MS-DIAL) and MS-FINDER softwares. The preprocessed data were sent to the GNPS to build a feature-based molecular network (FBMN). Thirty-three 4-quinolone alkaloids were annotated in the extracts and fractions of stems and roots, whereas 12 were annotated in the extracts and fractions of flowers and leaves. This represents an inaugural chemical investigation study employing UPLC-Q-TOF-MS/MS analysis, along with a molecular network approach, within this species and genus.

Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Isolation and Identification of Lichen Photobionts Collected from Different Environments in North of Portugal and Evaluation of Bioactivities of Their Extracts.

Lichens are organisms constituted by a symbiotic relationship between a fungus (mycobiont) and a photoautotrophic partner (photobiont). Lichens produce several bioactive compounds; however, the biotechnological exploitation of this organism is hampered by its slow growth. To start studying the possibility of exploiting lichens as alternative sources of bioactive compounds, eighteen lichens were collected in the north of Portugal in order to isolate and study the bioactivity of their photobionts. It was possible to isolate and cultivate only eight photobionts. Three of them, LFR1, LFA2 and LCF3, belong to the Coelastrella genus, the other two (LFA1 and LCF1) belong to the Chlorella genus and for the remaining three photobionts, LFS1, LCA1 and LCR1, it was impossible to isolate their microalgae. These only grow in consortium with bacteria and/or cyanobacteria. All extracts showed antioxidant activity, mainly at a concentration of 10 mg.mL-1. LFS1, a consortium extract, showed the highest antioxidant power, as well as the highest concentration of phenolic compounds (5.16 ± 0.53 mg of gallic acid equivalents (GAE).g-1). The extracts under study did not show significant antibacterial activity against Escherichia coli, Listeria or Salmonella. The Coelastrella sp. and LFA1 extracts showed the highest hyaluronidase inhibition. The LFR1 extract at a concentration of 5 mg.mL-1 showed the highest anti-inflammatory activity (79.77 ± 7.66%). The extracts of Coelastrella sp. and LFA1 also showed greater antidiabetic activity, demonstrating the high inhibitory power of α-amylase and α-glucosidase. LFR1 at a concentration of 5 mg.mL-1, due to its selective cytotoxicity inhibiting the growth of cancer cells (Caco-2 cells), is a promising anticancer agent.

Territorial Disparities in Dental Care for Disabled Persons and Oral Health-Related Indicators: A Population-Level Approach in Brazil's Public Healthcare System from 2014 to 2023.

This study evaluated territorial disparities in dental care for disabled persons in Brazil's public healthcare system from 2014 to 2023. The person-year incidence of outpatient dental procedures carried out by special care dentistry specialists and hospitalizations for dental procedures for disabled persons were compared across different regions and against the national estimate. In addition, productivity was correlated with oral health-related indicators. The significance level was set at 5%. The northern region exhibited the highest outpatient productivity, while the southern region showed lower productivity compared to the national estimate (both p-value < 0.05). This pattern was reversed in inpatient productivity (both p-value < 0.05), with the northeastern and central-western regions also below average (both p-value < 0.05). There were no significant correlations between the indicators and inpatient productivity, but outpatient productivity was positively correlated with the proportions of inhabitants who self-rated their general and oral health as "poor" or "very poor", who have never visited a dentist, and who visited a dentist for tooth extraction (all p-values < 0.05). Territorial disparities in dental care for disabled persons were observed within Brazil's public healthcare system, and they were correlated with unfavorable oral health-related indicators at the population level.

Reduced sympathetic activity is associated with the development of pain and muscle atrophy in a female rat model of fibromyalgia.

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.

Effect of preheating on the viscosity of composite resins.

Aim: To determine the effects of time and temperature on the viscosity of preheated composite resins. Materials and Methods: Eleven composite resins were heated to 60°C, and temperature analyses were performed at intervals of 1 min until they had cooled to 25°C. The permanent oscillatory shear test was performed at 25°C, 35°C, 50°C, and 60°C for three composite resins under a shear rate of 1s-1. One- and two-way analysis of variance were used for the analysis (α = 0.05). Results: There was no significant interaction between the composite resin and time (P = 0.9304), and only the main effect time was significantly different (P < 0.0001). A difference was observed between T0 and T6 (P < 0.001), but not after T7. The increase in temperature resulted in a viscosity reduction (P < 0.05). At 25°C, Beautifil II presented higher viscosity. Palfique LX5 showed a significant viscosity reduction with increasing temperature compared with the others (P < 0.05). For Beautifil II and Z100, there was no difference at temperatures of 50°C and 60°C, while for Palfique LX5, no statistical difference was observed at 35°C, 50°C, and 60°C. Conclusions: Ten minutes of preheating were sufficient to reach a temperature of 60°C, reducing viscosity by at least 84%. However, 5 min after removal, the composite resin cooled to room temperature. Clinical Significance: Preheating composite resin has potential benefits. To determine how this approach will work in clinical practice, it is important to define the effects of time and temperature in the protocol of this technique and understand its limitations.

Leukotriene receptor antagonists as adjuvant therapy of antihistamines in chronic urticaria: a systematic review and meta-analysis.

Certain guidelines recommend a second-generation H1-antihistamine (AH) as first-line treatment for patients with chronic urticaria (CU). However, some patients show insufficient response to a standard dose of this therapy and might benefit from adding leukotriene receptor antagonists (LTA). Therefore, we aimed to perform a systematic review and meta-analysis comparing LTA plus antihistamines with antihistamines alone. We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and Cochrane Central for randomized clinical trial (RCT) data comparing LTA plus AH treatment to AH alone in patients with CU. Statistical analysis was performed using R Studio 4.3.2. Heterogeneity was assessed with I2 statistics. Three studies comprising 234 patients with urticaria were included. The mean age was 37.23 years in the leukotriene antagonist + antihistamines (LTA + AH) group and 39.14 years in the antihistamines (AH) group. Follow-up ranged from 2 to 18 months between studies. There was no statistically significant difference between groups in terms of TSS level (SMD: -74.82; 95% CI: -222.66 to 73.02; P = 0.32; I2 = 98%), neither in terms of pruritus (MD: -0.07; 95% CI: -0.42 to 0.28; P = 0.70; I2 = 74%). After sensitivity analysis, with the systematic exclusion of each study from the grouped estimates, the result for TSS level did not change. These findings suggest that leukotriene receptor antagonists with antihistamines do not have better outcomes than antihistamines alone regarding TSS and pruritus in patients with CU.