"What really matters to the patients?": assessing the impact of wound healing on the quality of life in patients undergoing incisional hernia repair.

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.

Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of Plasmodium vivax in murine model.

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.

Vascular smooth muscle cells exhibit elevated hypoxia-inducible Factor-1α expression in human blood vessel organoids, influencing osteogenic performance.

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.

Validation of the carolinas comfort scale (CCS) in Brazil: a hernia-specific quality of life questionnaire.

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.

Weight Development and Growth Curves of Grazing Santa Inês Sheep Supplemented with Concentrate in the Pre-Weaning Phase.

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.

External validation of a nomogram for outcome prediction in management of medium-sized (1-2 cm) kidney stones.

BACKGROUND: Stone nomogram by Micali et al., able topredict treatment failure of shock-wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) in the management of single 1-2 cm renal stones, was developed on 2605 patients and showed a high predictive accuracy, with an area under ROC curve of 0.793 at internal validation. The aim of the present study is to externally validate the model to assess whether it displayed a satisfactory predictive performance if applied to different populations. METHODS: External validation was retrospectively performed on 3025 patients who underwent an active stone treatment from December 2010 to June 2021 in 26 centers from four countries (Italy, USA, Spain, Argentina). Collected variables included: age, gender, previous renal surgery, preoperative urine culture, hydronephrosis, stone side, site, density, skin-to-stone distance. Treatment failure was the defined outcome (residual fragments >4 mm at three months CT-scan). RESULTS: Model discrimination in external validation datasets showed an area under ROC curve of 0.66 (95% 0.59-0.68) with adequate calibration. The retrospective fashion of the study and the lack of generalizability of the tool towards populations from Asia, Africa or Oceania represent limitations of the current analysis. CONCLUSIONS: According to the current findings, Micali's nomogram can be used for treatment prediction after SWL, RIRS and PNL; however, a lower discrimination performance than the one at internal validation should be acknowledged, reflecting geographical, temporal and domain limitation of external validation studies. Further prospective evaluation is required to refine and improve the nomogram findings and to validate its clinical value.

Monitoring Bar Velocity to Quantify Fatigue in Resistance Training.

We analyzed the effects of load magnitude and bar velocity variables on sensitivity to fatigue. Seventeen resistance-trained men (age=25.7±4.9 years; height=177.0±7.2 cm; body mass=77.7±12.3 kg; back-squat 1RM=145.0±33.9 kg; 1RM/body mass=1.86) participated in the study. Pre- and post-exercise changes in the mean propulsive velocity (MPV) and peak velocity (PV) in the back-squat at different intensities were compared with variations in the countermovement jump (CMJ). CMJ height decreased significantly from pre- to post-exercise (∆%=-7.5 to -10.4; p<0.01; ES=0.37 to 0.60). Bar velocity (MPV and PV) decreased across all loads (∆%=-4.0 to -12.5; p<0.01; ES=0.32 to 0.66). The decrease in performance was similar between the CMJ, MPV (40% and 80% 1RM; p=1.00), and PV (80% 1RM; p=1.00). The magnitude of reduction in CMJ performance was greater than MPV (60% 1RM; p=0.05) and PV (40% and 60% 1RM; p<0.01) at the post-exercise moment. Low systematic bias and acceptable levels of agreement were only found between CMJ and MPV at 40% and 80% 1RM (bias=0.35 to 1.59; ICC=0.51 to 0.71; CV=5.1% to 8.5%). These findings suggest that the back-squat at 40% or 80% 1RM using MPV provides optimal sensitivity to monitor fatigue through changes in bar velocity.

Characterization of the fragmentation mechanisms in electrospray ionization tandem mass spectrometry of chloroquinoline derivatives with larvicidal activity against Aedes aegypti.

RATIONALE: 4,7-Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high-resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI-MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC50 values against Aedes aegypti larvae. METHODS: Five DCQ derivatives were synthesized by using previously described protocols. ESI-MS/MS analyses were carried out with a quadrupole/time-of-flight and ion-trap instrument. The proposed gas-phase protonation sites and fragmentation were supported by density functional theory calculations. The larvicidal tests were performed with the Ae. aegypti Rockefeller strain, and the LC50 values were determined by employing five test concentrations. Larval mortality was determined after treatment for 48 h. RESULTS: DCQ bromides or aldehydes (C-3 or C-8 positions), as well as the trimethylsilyl derivative (C-3 position), were prepared. Detailed ESI-MS/MS data revealed heteroatom elimination through an exception to the even-electron rule, to originate open-shell species. Computational studies were used to define the protonation sites and fragmentation pathways. High activity of DCQ and its derivatives against Ae. aegypti larvae was demonstrated. CONCLUSION: Our results provided a well-founded characterization of the fragmentation reactions of DCQ and its derivatives, which can be useful for complementary studies of the development of a larvicidal product against Ae. aegypti.

BMP7-induced osteoblast differentiation requires hedgehog signaling and involves nuclear mechanisms of gene expression control.

During the morphological changes occurring in osteoblast differentiation, Sonic hedgehog (Shh) plays a crucial role. While some progress has been made in understanding this process, the epigenetic mechanisms governing the expression of Hh signaling members in response to bone morphogenetic protein 7 (BMP7) signaling in osteoblasts remain poorly understood. To delve deeper into this issue, we treated pre-osteoblasts (pObs) with 100 ng/mL of BMP7 for up to 21 days. Initially, we validated the osteogenic phenotype by confirming elevated expression of well-defined gene biomarkers, including Runx2, Osterix, Alkaline Phosphatase (Alp), and bone sialoprotein (Bsp). Simultaneously, Hh signaling-related members Sonic (Shh), Indian (Ihh), and Desert (Dhh) Hedgehog (Hh) exhibited nuanced modulation over the 21 days in vitro period. Subsequently, we evaluated epigenetic markers, and our data revealed a notable change in the CpG methylation profile, considering the methylation/hydroxymethylation ratio. CpG methylation is a reversible process regulated by DNA methyltransferases and demethylases, including Ten-eleven translocation (Tets), which also exhibited changes during the acquisition of the osteogenic phenotype. Specifically, we measured the methylation pattern of Shh-related genes and demonstrated a positive Pearson correlation for GLI Family Zinc Finger 1 (Gli1) and Patched (Ptch1). This data underscores the significance of the epigenetic machinery in modulating the BMP7-induced osteogenic phenotype by influencing the activity of Shh-related genes. In conclusion, this study highlights the positive impact of epigenetic control on the expression of genes related to hedgehog signaling during the morphogenetic changes induced by BMP7 signaling in osteoblasts.

Intestinal microbiota diversity from broilers with runting and stunting syndrome performed by metagenomics.

RESEARCH HIGHLIGHTS: RSS causes dysbiosis of the gut microbiota of the ilea of chicks.A difference was found in gut microbiota between chicks with or without RSS.Candidatus Arthromitus was predominant in chicks with RSS.Clostridium sensu stricto 1 was strictly associated with chicks with RSS.

Effect of prednisolone in a kindling model of epileptic seizures in rats on cytokine and intestinal microbiota diversity.

Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures. Epileptic seizures can be initiated and facilitated by inflammatory mechanisms. As the dysregulation of the immune system would be involved in epileptogenesis, it is suggested that anti-inflammatory medications could impact epileptic seizures. These medications could potentially have a side effect by altering the structure and composition of the intestinal microbiota. These changes can disrupt microbial homeostasis, leading to dysbiosis and potentially exacerbating intestinal inflammation. We hypothesize that prednisolone may affect the development of epileptic seizures, potentially influencing the diversity of the intestinal microbiota and the regulation of pro-inflammatory cytokines in intestinal tissue. This study aimed to evaluate the effects of prednisolone treatment on epileptic seizures and investigate the effect of this drug on the bacterial diversity of the intestinal microbiota and markers of inflammatory processes in intestinal tissue. We used Male Wistar rat littermates (n = 31, 90-day-old) divided into four groups: positive control treated with 2 mg/kg of diazepam (n = 6), negative control treated with 0.9 g% sodium chloride (n = 6), and the remaining two groups were subjected to treatment with prednisolone, with one receiving 1 mg/kg (n = 9) and the other 5 mg/kg (n = 10). All administrations were performed intraperitoneally (i.p.) over 14 days. To induce the chronic model of epileptic seizures, we administered pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. Seizure latency (n = 6 - 10) and TNF-α and IL-1ß concentrations from intestinal samples were measured by ELISA (n = 6 per group), and intestinal microbiota was evaluated with intergenic ribosomal RNA (rRNA) spacer (RISA) analysis (n = 6 per group). The prednisolone treatment demonstrated an increase in the latency time of epileptic seizures and TNF-α and IL-1ß concentrations compared to controls. There was no statistically significant difference in intestinal microbiota diversity between the different treatments. However, there was a strong positive correlation between microbial diversity and TNF-α and IL-1ß concentrations. The administration of prednisolone yields comparable results to diazepam on increasing latency between seizures, exhibiting promise for its use in clinical studies. Although there were no changes in intestinal microbial diversity, the increase in the TNF-α and IL-1ß cytokines in intestinal tissue may be linked to immune system signaling pathways involving the intestinal microbiota. Additional research is necessary to unravel the intricacies of these pathways and to understand their implications for clinical practice.

Analysis of modified ilib therapy in patients submitted to plastic surgery.

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.

Seroepidemiological survey to cell culture rabies vaccines (CCRV) in Brazil.

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.

Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success.

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

Adora2A downregulation promotes caffeine neuroprotective effect against LPS-induced neuroinflammation in the hippocampus.

Caffeine has been extensively studied in the context of CNS pathologies as many researchers have shown that consuming it reduces pro-inflammatory biomarkers, potentially delaying the progression of neurodegenerative pathologies. Several lines of evidence suggest that adenosine receptors, especially A1 and A2A receptors, are the main targets of its neuroprotective action. We found that caffeine pretreatment 15 min before LPS administration reduced the expression of Il1b in the hippocampus and striatum. The harmful modulation of caffeine-induced inflammatory response involved the downregulation of the expression of A2A receptors, especially in the hippocampus. Caffeine treatment alone promoted the downregulation of the adenosinergic receptor Adora2A; however, this promotion effect was reversed by LPS. Although administering caffeine increased the expression of the enzymes DNA methyltransferases 1 and 3A and decreased the expression of the demethylase enzyme Tet1, this effect was reversed by LPS in the hippocampus of mice that were administered Caffeine + LPS, relative to the basal condition; no significant differences were observed in the methylation status of the promoter regions of adenosine receptors. Finally, the bioinformatics analysis of the expanded network demonstrated the following results: the Adora2B gene connects the extended networks of the adenosine receptors Adora1 and Adora2A; the Mapk3 and Esr1 genes connect the extended Adora1 network; the Mapk4 and Arrb2 genes connect the extended Adora2A network with the extended network of the proinflammatory cytokine Il1ß. These results indicated that the anti-inflammatory effects of acute caffeine administration in the hippocampus may be mediated by a complex network of interdependencies between the Adora2B and Adora2A genes.

Plasma Jet versus Electrocarbonization in the Treatment of Wrinkles of the Upper Palpebral Region.

Background: The plasma jet is a non-surgical and minimally invasive procedure that acts by heating the superficial region of the skin, providing rejuvenation of the region. Objective: We sought to compare the clinical and histological effects of direct plasma jet versus electrocarbonization without plasma in the treatment of wrinkles in the upper palpebral region. Methods: This is a clinical trial in which 20 volunteers participated and divided into two groups: electrocarbonization (EG) and plasma jet (JPG), which were clinically evaluated before and after treatment through evaluation protocols, photographs, and questionnaires. Three treatment sessions were performed in the upper eyelid region with an interval of 30 days. After the treatment, a surgical procedure of upper blepharoplasty was performed on two volunteers to remove a skin fragment and later histological analysis. Results: The JPG showed better clinical responses in rejuvenation. The EG promoted an increase in the number of fibroblasts, the number of blood vessels and the amount of inflammation. The JPG showed an increase in the number of fibroblasts and blood vessels. It was observed that the JPG generated activation of T lymphocytes (CD3), macrophages (CD68), and plasmocytes (CD138); in addition to reducing the number of positive cells for CD57 (NK cells). The satisfaction analysis shows that 100 percent in the JPG considered themselves satisfied with the treatment. Conclusion: We verified that in comparison with electrocarbonization, the use of a direct plasma jet promoted tissue improvement at the histological level, in addition to fewer adverse reactions.

Epigenetic changes in shear-stressed endothelial cells.

Epigenetic changes, particularly histone compaction modifications, have emerged as critical regulators in the epigenetic pathway driving endothelial cell phenotype under constant exposure to laminar forces induced by blood flow. However, the underlying epigenetic mechanisms governing endothelial cell behavior in this context remain poorly understood. To address this knowledge gap, we conducted in vitro experiments using human umbilical vein endothelial cells subjected to various tensional forces simulating pathophysiological blood flow shear stress conditions, ranging from normotensive to hypertensive forces. Our study uncovers a noteworthy observation wherein endothelial cells exposed to high shear stress demonstrate a decrease in the epigenetic marks H3K4ac and H3K27ac, accompanied by significant alterations in the levels of HDAC (histone deacetylase) proteins. Moreover, we demonstrate a negative regulatory effect of increased shear stress on HOXA13 gene expression and a concomitant increase in the expression of the long noncoding RNA, HOTTIP, suggesting a direct association with the suppression of HOXA13. Collectively, these findings represent the first evidence of the role of histone-related epigenetic modifications in modulating chromatin compaction during mechanosignaling of endothelial cells in response to elevated shear stress forces. Additionally, our results highlight the importance of understanding the physiological role of HOXA13 in vascular biology and hypertensive patients, emphasizing the potential for developing small molecules to modulate its activity. These findings warrant further preclinical investigations and open new avenues for therapeutic interventions targeting epigenetic mechanisms in hypertensive conditions.

Biomechanical influence of narrow-diameter implants placed at the crestal and subcrestal level in the maxillary anterior region. A 3D finite element analysis.

PURPOSE: To evaluate the tendency of movement, stress distribution, and microstrain of single-unit crowns in simulated cortical and trabecular bone, implants, and prosthetic components of narrow-diameter implants with different lengths placed at the crestal and subcrestal levels in the maxillary anterior region using 3D finite element analysis (FEA). MATERIALS AND METHODS: Six 3D models were simulated using Invesalius 3.0, Rhinoceros 4.0, and SolidWorks software. Each model simulated the right anterior maxillary region including a Morse taper implant of Ø2.9 mm with different lengths (7, 10, and 13 mm) placed at the crestal and subcrestal level and supporting a cement-retained monolithic single crown in the area of tooth 12. The FEA was performed using ANSYS 19.2. The simulated applied force was 178 N at 0°, 30°, and 60°. The results were analyzed using maps of displacement, von Mises (vM) stress, maximum principal stress, and microstrain. RESULTS: Models with implants at the subcrestal level showed greater displacement. vM stress increased in the implant and prosthetic components when implants were placed at the subcrestal level compared with the crestal level; the length of the implants had a low influence on the stress distribution. Higher stress and strain concentrations were observed in the cortical bone of the subcrestal placement, independent of implant length. Non-axial loading influenced the increased stress and strain in all the evaluated structures. CONCLUSIONS: Narrow-diameter implants positioned at the crestal level showed a more favorable biomechanical behavior for simulated cortical bone, implants, and prosthetic components. Implant length had a smaller influence on stress or strain distribution than the other variables.

Suction in Percutaneous Nephrolithotripsy: Evolution, Development, and Outcomes from Experimental and Clinical studies. Results from a Systematic Review.

CONTEXT: Controversy exists regarding the therapeutic benefit of suction use during percutaneous nephrolithotripsy (PCNL). OBJECTIVE: To review and highlight the options available in the use of suction for PCNL, and to discuss their strengths and limitations. EVIDENCE ACQUISITION: A systematic literature search was performed using Scopus, EMBASE, and PubMed. Thirty four studies were included. There was one ex vivo study. Among clinical studies, 24 used a vacuum/suctioning sheath and nine a handpiece suction device/direct-in-scope suction. The suction technique was employed in standard, mini-PCNL, supermini-PCNL, and enhanced supermini­PCNL techniques. EVIDENCE SYNTHESIS: Handpiece suction devices demonstrated better safety and efficiency in treating large stones than nonsuction PCNL and in a much shorter time. Trilogy and ShockPulse-SE were equally effective, safe, and versatile for standard PCNL and mini-PCNL. The heavier handpiece makes Trilogy less ergonomically friendly. Laser suction handpiece devices can potentiate laser lithotripsy by allowing for better laser control with simultaneous suction of small fragments and dust. Integrated suction-based sheaths are available in reusable and disposable forms for mini-PCNL only. Mini-PCNL with suction reported superior outcomes for operative time and stone-free rate to mini-PCNL. This also helped minimize infectious complications by a combination of intrarenal pressure reduction and faster aspiration of irrigation fluid reducing the risk of sepsis, enhance intraoperative vision, and improve lithotripsy efficiency, which makes it a very attractive evolution for PCNL. CONCLUSIONS: Suction devices in PCNL are reforming the way PCNL is being done. Adding suction to mini-PCNL reduces infectious complications and improves the stone-free rate. Our review shows that despite the limited evidence, suction techniques appear to improve PCNL outcomes. PATIENT SUMMARY: In this review, we looked at the intra- and perioperative outcomes of percutaneous nephrolithotripsy (PCNL) with the addition of suction. With better stone fragmentation and fewer postoperative infections, this technology is very useful particularly for mini-PCNL.

Labelling of intravenous drug delivery devices in critically ill patients: A scoping review.

BACKGROUND: Labelling is a strategy that contributes to the correct and faster identification of drugs, minimizing misidentification. There is a gap in knowledge on optimal labelling standards for intravenous (IV) devices applied to the care of critically ill patients. AIM: The goal of this article was to map existing knowledge on the labelling of IV drug delivery devices in critically ill patients for the prevention of medication errors. STUDY DESIGN: This was a scoping review conducted according to the JBI methodology in the LILACS, MEDLINE, CINAHL, IBECS, Scopus, Embase and Web of Science databases, and on the websites of specialized institutions. Searches were conducted up to December 2022 for scientific articles and grey literature that addressed the labelling of IV devices in intensive care units, emergency departments, and anaesthesia units. The data were collected using a structured form and were later classified, summarized, and aggregated to map the knowledge related to the review question. RESULTS: Twenty-one documents were included, which demonstrated variability in label use with IV drug delivery devices. The following features of structure and design stood out: printed format, colour coding, letter size differentiation, and the use of sturdy material. In terms of information, the name of the drug, dose, date and time of preparation, identification of the patient, and who prepared it were found. CONCLUSIONS: The identified patterns contributed to the reduction of drug misidentification and the development of timelier drug labelling and administration. RELEVANCE TO CLINICAL PRACTICE: The evidence supports the development of standardized labels for the prevention of medication errors.