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PURPOSE: To assess the role of dexmedetomidine as an adjuvant to local anesthetics (LA) in enhancing the duration and quality of peribulbar blocks for ophthalmic surgeries. DESIGN: Systematic review with meta-analysis and trial sequential analysis Methods: We systematically searched MEDLINE, Embase, and Cochrane for randomized controlled trials (RCTs) involving adult patients undergoing ophthalmic surgery under peribulbar block, comparing LA alone versus LAâ¯+â¯dexmedetomidine. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were computed using a random effects model. Sensitivity and trial-sequential analyses (TSA) were performed to assess inconsistencies, weight type II and II errors, and estimate the required information size of the samples for all endpoints. RESULTS: Sixteen RCTs (1,220 patients) were included. Compared with LA alone, dexmedetomidine was associated with prolonged (1) motor block duration (MD 65.01 minutes, p<0.001) and (2) sensory block duration (MD 81.94 minutes, p<0.001); (3) reduced intraocular pressure (IOP) (MD -2.6 mmHg, p<0.001), and (4) decreased need for supplemental injections (RR 0.44, p=0.007). Additionally, dexmedetomidine showed (5) longer time to analgesic request (MD 97.15 minutes, p<0.001) and (6) increased surgeon satisfaction (RR 1.52, p=0.01). Sensitivity analyses and TSA were consistent across all endpoints, and the required information size was achieved for most endpoints, indicating that pooled analyses were reliable and sample sizes were sufficient. CONCLUSIONS: Compared with LA alone, dexmedetomidine significantly prolonged sensory and motor block duration and the time to the first analgesic request; decreased IOP and the need for supplemental injections, while increasing surgeon satisfaction.
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Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1ß and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety.
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Ansiedade , Eixo Encéfalo-Intestino , Disfunção Cognitiva , Depressão , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Peptídeos Semelhantes ao Glucagon , Camundongos Endogâmicos C57BL , Animais , Peptídeos Semelhantes ao Glucagon/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/metabolismo , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Depressão/tratamento farmacológico , Depressão/psicologia , Depressão/metabolismo , Masculino , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Ansiedade/etiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/psicologia , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Antidepressivos/farmacologia , Antidepressivos/uso terapêuticoRESUMO
(1) Objective: The aim of this study was to assess the biological behavior of bone tissue on a machined surface (MS) and modifications made by a laser beam (LS) and by a laser beam incorporated with hydroxyapatite (HA) using a biomimetic method without thermic treatment (LHS). (2) Methods: Scanning electron microscopy coupled with energy-dispersive X-ray spectrometry (SEM/EDX) was performed before and after installation in the rabbit tibiae. A total of 20 Albinus rabbits randomly received 30 implants of 3.75 × 10 mm in the right and left tibias, with two implants on each surface in each tibia. In the animals belonging to the 4-week euthanasia period group, intramuscular application of the fluorochromes calcein and alizarin was performed. In implants placed mesially in the tibiofemoral joint, biomechanical analysis was performed by means of a removal torque (N/cm). The tibias with the implants located distally to the joint were submitted for analysis by confocal laser microscopy (mineral apposition rate) and for histometric analysis by bone contact implant (%BIC) and newly formed bone area (%NBA). (3) Results: The SEM showed differences between the surfaces. The biomechanical analysis revealed significant differences in removal torque values between the MSs and LHSs over a 2-week period. Over a 4-week period, both the LSs and LHSs demonstrated removal torque values statistically higher than the MSs. BIC of the LHS implants were statistically superior to MS at the 2-week period and LHS and LS surfaces were statistically superior to MS at the 4-week period. Statistical analysis of the NBA of the implants showed difference between the LHS and MS in the period of 2 weeks. (4) Conclusions: The modifications of the LSs and LHSs provided important physicochemical modifications that favored the deposition of bone tissue on the surface of the implants.
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In the Americas, P. vivax is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.
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Anticorpos Antiprotozoários , Antígenos de Protozoários , Vacinas Antimaláricas , Malária Vivax , Camundongos Endogâmicos BALB C , Plasmodium vivax , Proteínas de Protozoários , Animais , Plasmodium vivax/imunologia , Plasmodium vivax/genética , Camundongos , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/genética , Malária Vivax/imunologia , Malária Vivax/prevenção & controle , Anticorpos Antiprotozoários/imunologia , Vacinas Antimaláricas/imunologia , Feminino , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Modelos Animais de Doenças , Adjuvantes Imunológicos , Imunogenicidade da Vacina , Antígenos de SuperfícieRESUMO
PURPOSE: We aim to evaluate the impact of surgical wound complications in the first 30 postoperative days after incisional hernia repair on the long-term quality of life of patients. In addition, the impact of the surgical technique and preoperative comorbidities on the quality of life of patients will also be evaluated. METHOD: Prospective cohort study, which evaluates 115 patients who underwent incisional hernioplasty between 2019 and 2020, using the onlay and retromuscular techniques. These patients were initially assessed with regard to surgical wound outcomes in the first 30 postoperative days (surgical site infection (SSI) or surgical site occurrence (SSO)), and then, assessed after three years, through a specific quality of life questionnaire, the Hernia Related Quality of Life Survey (HerQLes). RESULTS: After some patients were lost to follow-up during the study period, due to death, difficulty in contact, refusal to respond to the questionnaire, eighty patients were evaluated. Of these, 11 patients (13.8%) had SSI in the first 30 postoperative days and 37 (46.3%) had some type of SSO. The impact of both SSI and SSO on quality of life indices was not identified. When analyzing others variables, we observed that the Body Mass Index (BMI) had a significant impact on the patients' quality of life. Likewise, hernia size and mesh size were identified as variables related to a worse quality of life outcome. No difference was observed regarding the surgical techniques used. CONCLUSION: In the present study, no relationship was identified between surgical wound outcomes (SSO and SSI) and worse quality of life results using the HerQLes score. We observed that both BMI and the size of meshes and hernias showed an inversely proportional relationship with quality of life indices. However, more studies evaluating preoperative quality of life indices and comparing them with postoperative indices should be carried out to evaluate these correlations.
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Herniorrafia , Hérnia Incisional , Qualidade de Vida , Infecção da Ferida Cirúrgica , Cicatrização , Humanos , Feminino , Masculino , Hérnia Incisional/cirurgia , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Cicatrização/fisiologia , Inquéritos e Questionários , Adulto , Telas Cirúrgicas , Estudos de CoortesRESUMO
Considering the importance of alternative methodologies to animal experimentation, we propose an organoid-based biological model for in vitro blood vessel generation, achieved through co-culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (α-SMA + cells) at the periphery and endothelial cells (CD31+ cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1α expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1α to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1α.
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Subunidade alfa do Fator 1 Induzível por Hipóxia , Músculo Liso Vascular , Miócitos de Músculo Liso , Organoides , Osteogênese , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Osteogênese/genética , Organoides/metabolismo , Organoides/citologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/citologia , Células Cultivadas , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/citologia , Vasos Sanguíneos/crescimento & desenvolvimento , Técnicas de Cocultura/métodos , Diferenciação Celular , Células Endoteliais/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologiaRESUMO
INTRODUCTION: Ventral hernia surgery (VHS) has the intent to promote a better quality of life (QoL). VHS results were evaluated by recurrence incidence in the past, however the concept of Patient-Reported Outcomes Measures has changed this scenario. SF-36 is a generic questionnaire with some limitations on the hernioplasty postoperative evaluation. Disease-specific surveys such Hernia-Related Quality of Life Survey (HerQLes) and Carolinas Comfort Scale (CCS) were developed to improve specificity. The aim of this study was to validate a Brazilian version of the CCS as a QoL questionnaire for patients undergoing VHS in Brazil. MATERIALS AND METHODS: The study consists of a retrospective cohort that reviewed the medical records of patients who underwent ventral hernia surgery for incisional hernias in the Hospital de Clínicas de Porto Alegre between January 2019 to December 2020. Participants answered both the HerQles questionnaire and the CCS, then we compared the patients' scores between scales. In-personal evaluations or surveys applied by telemedicine were performed. Intraclass correlation coefficient was utilized to assess the consistency of the agreement between the HerQLes and CCS scales. RESULTS: A sample of 80 patients were evaluated. Most were male (70%), mean age 61.11 years and BMI 28.4. The most common comorbidity was systemic arterial hypertension, one third were smokers and 77.5% of cases were ASA 2. The average HerQLes score was 30.40 and the CCS was 15.46 (SD: 21.81), with an intraclass coefficient of 0.68. CONCLUSION: This study suggests that CCS is a good and robust tool for assessing ventral hernia. Tools to measure QoL are increasingly used in the literature, as QoL seems to be important data to assess surgical success, since it shows the perception of the patient about the results of their surgery. Further studies with larger sample sizes should be performed to confirm our findings.
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Monitoring weight development is essential for decision-making and assessing the effectiveness of management strategies. However, this practice is often hindered by the lack of scales on farms. This study aimed to characterize the weight development and growth curves of male and female Santa Inês lambs from birth to weaning, managed on pasture with creep-fed concentrate supplementation. Data from 212 lambs during the pre-weaning phase were analyzed. The animals were weighed every seven days to evaluate total weight gain and average daily gain. Biometric measurements were taken every 28 days. Mixed models were used to assess the effects of sex and birth type on birth and weaning weights. Simple and multiple linear regression models were employed to estimate live weight using biometric measurements. The non-linear Gompertz model was utilized to describe weight development and formulate growth curves. Results were considered significant at p < 0.05. An interaction effect between birth type and sex (p < 0.05) was noted for birth weight, with the lowest weight observed in twin-birth females (2.96 kg) and the highest in single-birth males (3.73 kg) and females (3.65 kg) (p > 0.05). Birth type significantly influenced average daily gain, total weight gain, and weaning weight (p < 0.05). The Gompertz model accurately depicted the growth curves, effectively describing the weight development. Pearson's correlation coefficients between biometric measurements and weight were positive and significant (p < 0.05), ranging from 0.599 for hip height to 0.847 for heart girth. Consequently, the simple and multiple regression equations demonstrated high precision in predicting weaning weight. In conclusion, twin-birth lambs receiving concentrate supplementation via creep-feeding and managed on pasture showed different developmental patterns compared to single-birth lambs under the same conditions. The Gompertz model proved effective for monitoring development during the pre-weaning phase. All simple and multiple linear regression models were effective in predicting weaning weight through biometric measurements. However, for practical application, the model incorporating two measurements-body length and abdominal circumference-is recommended.
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Rabies is a contagious viral disease that can be easily transmitted by the saliva and brain/nervous system tissues of the infected animals, causing severe and fatal encephalitis in both animals and humans. Vaccination campaigns are crucial to combat and prevent rabies's spread in dogs and humans. The Modified Fuenzalida & Palicios vaccines have been widely used since the 70s and have proven effective in producing a solid serological response. Since 2008, the Brazilian Ministry of Health has introduced a Cell Culture Rabies Vaccine (CCRV) for all dog mass vaccination campaigns in Brazil. However, to date, there is limited evidence on the immunologic response of dogs to this type of vaccine in field conditions. The present study evaluated the serological response in dogs vaccinated with CCRV from blood samples of 724 dogs using the Simplified Fluorescence Inhibition Microtest - SFIMT. Dogs with a titer equal to 0.5 IU/mL or above were considered seropositive. The results revealed that 59.12% (428/724) of all dogs tested and 48.49% (32/66) of primo-vaccinated animals were seropositive. The percentage of seronegative animals was higher than seropositive for animals that received a single dose during their life (p < 0.05). The opposite was observed in animals with five or more doses. The results of this study demonstrated that the CCRV vaccines elicit a satisfactory immunological response in field conditions and can constitute an essential population-level preventive strategy as part of annual canine rabies vaccination campaigns. Although its effectiveness has been studied, there is limited evidence of its immunological response in dogs under field conditions. This paper evaluates the serological response to CCRV in dogs vaccinated during mass vaccination campaigns from 2012 to 2017.
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The sample comprised 44 volunteers who had undergone some surgical procedure and were equally divided into four groups. G1 started the therapy 24 h after the surgical procedure with the device off. G2 followed the same time pattern, 24 h, but with the device turned on. G3 and G4 started therapy three days after the surgical procedure; in G3, the device was turned off, and in G4, the device remained on during therapy; each session lasted 30 min, using 660 nm (red), energy 180 J. For all groups, the therapy started with daily use for seven days and followed the interval use of three times a week until completed 21 days. The revaluation was performed after 7 and 21 days. The results found show changes in HR at rest, systolic and diastolic BP, and in peripheral oxygen saturation, which showed a significant difference in the groups that used on-therapy (p < 0.05). In the MCGILL Scale evaluation, the mean total score showed a more accentuated drop in the groups that used ILIB, (p < 0.05). ILIB may have prevented a more significant evolution of firosis levels; however, no changes were observed in the evaluation of sleep and anxiety. The application of the ILIB in patients undergoing plastic surgery was supported in terms of hemodynamics and pain; in addition, starting the ILIB application 24 h after the procedure proved to be more advantageous.