Assessment of inbreeding coefficients and inbreeding depression on complex traits from genomic and pedigree data in Nelore cattle.

BACKGROUND: Nelore cattle play a key role in tropical production systems due to their resilience to harsh conditions, such as heat stress and seasonally poor nutrition. Monitoring their genetic diversity is essential to manage the negative impacts of inbreeding. Traditionally, inbreeding and inbreeding depression are assessed by pedigree-based coefficients (F), but recently, genetic markers have been preferred for their precision in capturing the inbreeding level and identifying animals at risk of reduced productive and reproductive performance. Hence, we compared the inbreeding and inbreeding depression for productive and reproductive performance traits in Nelore cattle using different inbreeding coefficient estimation methods from pedigree information (FPed), the genomic relationship matrix (FGRM), runs of homozygosity (FROH) of different lengths (> 1 Mb (genome), between 1 and 2 Mb - FROH 1-2; 2-4 Mb FROH 2-4 or > 8 Mb FROH >8) and excess homozygosity (FSNP). RESULTS: The correlation between FPed and FROH was lower when the latter was based on shorter segments (r = 0.15 with FROH 1-2, r = 0.20 with FROH 2-4 and r = 0.28 with FROH 4-8). Meanwhile, the FPed had a moderate correlation with FSNP (r = 0.47) and high correlation with FROH >8 (r = 0.58) and FROH-genome (r = 0.60). The FROH-genome was highly correlated with inbreeding based on FROH>8 (r = 0.93) and FSNP (r = 0.88). The FGRM exhibited a high correlation with FROH-genome (r = 0.55) and FROH >8 (r = 0.51) and a lower correlation with other inbreeding estimators varying from 0.30 for FROH 2-4 to 0.37 for FROH 1-2. Increased levels of inbreeding had a negative impact on the productive and reproductive performance of Nelore cattle. The unfavorable inbreeding effect on productive and reproductive traits ranged from 0.12 to 0.51 for FPed, 0.19-0.59 for FGRM, 0.21-0.58 for FROH-genome, and 0.19-0.54 for FSNP per 1% of inbreeding scaled on the percentage of the mean. When scaling the linear regression coefficients on the standard deviation, the unfavorable inbreeding effect varied from 0.43 to 1.56% for FPed, 0.49-1.97% for FGRM, 0.34-2.2% for FROH-genome, and 0.50-1.62% for FSNP per 1% of inbreeding. The impact of the homozygous segments on reproductive and performance traits varied based on the chromosomes. This shows that specific homozygous chromosome segments can be signs of positive selection due to their beneficial effects on the traits. CONCLUSIONS: The low correlation observed between FPed and genomic-based inbreeding estimates suggests that the presence of animals with one unknown parent (sire or dam) in the pedigree does not account for ancient inbreeding. The ROH hotspots surround genes related to reproduction, growth, meat quality, and adaptation to environmental stress. Inbreeding depression has adverse effects on productive and reproductive traits in Nelore cattle, particularly on age at puberty in young bulls and heifer calving at 30 months, as well as on scrotal circumference and body weight when scaled on the standard deviation of the trait.

Genotype-by-environment interactions in beef and dairy cattle populations: A review of methodologies and perspectives on research and applications.

Modern livestock production systems are characterized by a greater focus on intensification, involving managing larger numbers of animals to achieve higher productive efficiency and animal health and welfare within herds. Therefore, animal breeding programs need to be strategically designed to select animals that can effectively enhance production performance and animal welfare across a range of environmental conditions. Thus, this review summarizes the main methodologies used for assessing the levels of genotype-by-environment interaction (G × E) in cattle populations. In addition, we explored the importance of integrating genomic and phenotypic information to quantify and account for G × E in breeding programs. An overview of the structure of cattle breeding programs is provided to give insights into the potential outcomes and challenges faced when considering G × E to optimize genetic gains in breeding programs. The role of nutrigenomics and its impact on gene expression related to metabolism in cattle are also discussed, along with an examination of current research findings and their potential implications for future research and practical applications. Out of the 116 studies examined, 60 and 56 focused on beef and dairy cattle, respectively. A total of 83.62% of these studies reported genetic correlations across environmental gradients below 0.80, indicating the presence of G × E. For beef cattle, 69.33%, 24%, 2.67%, 2.67%, and 1.33% of the studies evaluated growth, reproduction, carcass and meat quality, survival, and feed efficiency traits, respectively. By contrast, G × E research in dairy cattle populations predominantly focused on milk yield and milk composition (79.36% of the studies), followed by reproduction and fertility (19.05%), and survival (1.59%) traits. The importance of G × E becomes particularly evident when considering complex traits such as heat tolerance, disease resistance, reproductive performance, and feed efficiency, as highlighted in this review. Genomic models provide a valuable avenue for studying these traits in greater depth, allowing for the identification of candidate genes and metabolic pathways associated with animal fitness, adaptation, and environmental efficiency. Nutrigenetics and nutrigenomics are emerging fields that require extensive investigation to maximize our understanding of gene-nutrient interactions. By studying various transcription factors, we can potentially improve animal metabolism, improving performance, health, and quality of products such as meat and milk.

Genotype-by-environment interactions for feed efficiency traits in Nellore cattle based on bi-trait reaction norm models.

BACKGROUND: Selecting animals for feed efficiency directly impacts the profitability of the beef cattle industry, which contributes to minimizing the environmental footprint of beef production. Genetic and environmental factors influence animal feed efficiency, leading to phenotypic variability when exposed to different environmental conditions (i.e., temperature and nutritional level). Thus, our aim was to assess potential genotype-by-environment (G × E) interactions for dry matter intake (DMI) and residual feed intake (RFI) in Nellore cattle (Bos taurus indicus) based on bi-trait reaction norm models (RN) and evaluate the genetic association between RFI and DMI across different environmental gradient (EG) levels. For this, we used phenotypic information on 12,958 animals (young bulls and heifers) for DMI and RFI recorded during 158 feed efficiency trials. RESULTS: The heritability estimates for DMI and RFI across EG ranged from 0.26 to 0.54 and from 0.07 to 0.41, respectively. The average genetic correlations (± standard deviation) across EG for DMI and RFI were 0.83 ± 0.19 and 0.81 ± 0.21, respectively, with the lowest genetic correlation estimates observed between extreme EG levels (low vs. high) i.e. 0.22 for RFI and 0.26 for DMI, indicating the presence of G × E interactions. The genetic correlation between RFI and DMI across EG levels decreased as the EG became more favorable and ranged from 0.79 (lowest EG) to 0.52 (highest EG). Based on the estimated breeding values from extreme EG levels (low vs. high), we observed a moderate Spearman correlation of 0.61 (RFI) and 0.55 (DMI) and a selection coincidence of 53.3% and 40.0% for RFI and DMI, respectively. CONCLUSIONS: Our results show evidence of G × E interactions on feed efficiency traits in Nellore cattle, especially in feeding trials with an average daily gain (ADG) that is far from the expected of 1 kg/day, thus increasing reranking of animals.

Assessing Brazilian Medical Student Awareness About Global Surgery: A Survey-Based Study.

BACKGROUND: Global surgery is an interdisciplinary field that advocates for access to equitable, affordable surgical services for all people. Engaging medical students in the field can strengthen the surgical workforce in low- and middle-income countries. We aim to investigate Brazilian medical students' acknowledgment of global surgery and their preferred learning platforms. MATERIALS AND METHODS: We performed a cross-sectional study through an anonymous Portuguese survey on Google Forms, consisting of 30 mixed multiple-choice and five-point Likert scale questions. Students enrolled in a Brazilian medical school from the second to sixth academic year fulfilled inclusion criteria. The association between qualitative variables was assessed using Chi-square, Fisher's exact test, or binary logistic model. RESULTS: We received 1,345 responses from 208 medical schools. Only 20.9% (282/1,345) of participants reported awareness of global surgery, who were predominantly female. 96.5% (1,298/1,345) declared interest in knowing more about global surgery and participants indicated social media (71.6%, 202/282) as the prevalent manner to gain awareness on it, followed by webinars (63.5%, 179/282). Extracurricular classes were the most preferable option among students (61.4%, 827/1,345) to get acquainted with the field, followed by internships (59.4%, 812/1,345), workshops (57%, 767/1,345), and social media (53.4%, 730/1,345). The main obstacles to pursue a global surgery career were lack of national opportunities (32%, 431/1,345) and adequate training (25.4%, 341/1,345). CONCLUSION: We outlined the most strategic pathways to raising awareness on global surgery among Brazilian medical students, providing relevant insights on its education in similar settings.

Deproteinized bovine bone mineral is non-inferior to deproteinized bovine bone mineral with 10% collagen in maintaining the soft tissue contour post-extraction: A randomized trial.

OBJECTIVES: To test the non-inferiority of demineralized bovine bone mineral (DBBM) compared to demineralized bovine bone mineral with 10% collagen (DBBM-C) for the maintenance of the soft tissue contour after tooth extraction in the esthetic zone. MATERIAL AND METHODS: Sixty-five patients randomly received ridge preservation at a single site in the anterior maxilla with DBBM or DBBM-C. Both, DBBM and DBBM-C, were covered with a collagen matrix. Profilometric analyses were performed at baseline (BL), immediately after treatment (PO), and at 4 months (FU; day of implant placement). The main outcome was the horizontal mean change (HC) at the buccal aspect. The measurements also included changes of the estimated soft tissue thickness (eTT) at 1, 3, and 5 mm below the buccal gingival margin. Descriptive analysis was performed, and differences between groups were analyzed using independent samples t test. The non-inferiority test was performed for HC. RESULTS: At 4 months, the horizontal mean change (HC) was -1.43 mm (±0.53 mm) (DBBM-C) and -1.32 mm (±0.53 mm) (DBBM). Change of the estimated soft tissue thickness (eTT) between baseline (BL) and four months of follow-up (FU) at 1, 3, and 5 mm amounted to -4.58 mm (±2.02 mm), -2.40 mm (±0.97 mm), and -1.37 mm (±0.78 mm) for DBBM-C and to -4.12 mm (±1.80 mm), -2.09 mm (±0.91 mm), and -1.23 mm (±0.72 mm) for DBBM. The differences between the groups were not statistically significantly for any of the outcome measures (p > .05). CONCLUSIONS: DBBM is non-inferior to DBBM-C for the maintenance of the soft tissue contour 4 months after tooth extraction.

The positive effect of tenting screws for primary horizontal guided bone regeneration: A retrospective study based on cone-beam computed tomography data.

OBJECTIVES: To radiographically evaluate the effect of the adjunctive use of tenting screws (TS) for primary horizontal guided bone regeneration (GBR). MATERIALS & METHODS: Twenty-eight patients in need of staged bone augmentation were consecutively treated in a private practice. A xenogenic particulate bone substitute material (DBBM) and a resorbable collagen membrane were used in all patients. Subjects were divided into two groups: control (conventional GBR; n = 22) and test (tenting screws in conjunction with GBR - TS; n = 22). CBCT images were obtained before augmentation and after 6-8 months. CBCTs were superimposed, and linear horizontal measurements were performed. Alveolar ridge width (RW) and ridge width change (RWchange) were assessed at 1, 3, 5, and 7 mm below the bone crest. RESULTS: Forty-four sites in 28 patients were evaluated. No differences between the groups were detected for RW at baseline (TS: 5.87 ± 2.41; control: 5.36 ± 1.65). Regarding RWchange, TS promoted an additional effect at 1 and 3 mm below the crest compared to control (p < .05; RWchange-1 TS: 3.72 ± 2.46; control: 1.25 ± 3.05; RWchange-3 TS: 3.98 ± 2.53; control: 2.50 ± 2.02). The final RW was greater in group TS compared to the control group at the 1, 3, and 5 mm level (p < .05). CONCLUSIONS: The use of tenting screws exerted a positive effect on staged GBR with a greater final RW at the 3 mm level. In addition, GBR in conjunction with TS was able to provide consistent bone augmentation at lingual/palatal sites.

Profilometric changes of peri-implant tissues over 5 years: A randomized controlled trial comparing a one- and two-piece implant system.

OBJECTIVES: To assess the profilometric changes of the buccal soft tissues between baseline and 5 years of loading using a one- and two-piece dental implant system. MATERIALS AND METHODS: Sixty patients randomly received dental implants of either a two-piece type (BRA) or a one-piece type (STM). Casts were obtained at baseline (after crown insertion), at the 1-year and at the 5-year follow-up. Stereolithography files were obtained from the casts for digital superimposition. One implant and the contralateral natural tooth were selected for the analysis. Thirty-three patients (BRA = 16; STM = 17) were included. Measurements included changes for crown height (CH) and estimated soft tissue thickness, as well as the profilometric change at the implant and the tooth site. Nonparametric methods were applied for the statistical analyses and medians and quartiles presented. RESULTS: The BRA group lost -0.39 mm and the STM group lost -0.40 mm of volume between baseline and the 5-year follow-up at the implant site (p > 0.05). The tooth site lost -0.18 mm (BRA) and -0.12 mm (STM) (p > 0.05). Volume differences between implants and teeth amounted to -0.05 mm (baseline to 1 year) and -0.25 mm (baseline to 5 years) for BRA, while for STM, the values were 0.03 mm (baseline to 1 year) and -0.16 mm (baseline to 5 years). The changes for implant CH at 1 and 5 years of follow-up amounted 0.10 and 0.09 mm (BRA) and to 0.03 and 0.22 mm (STM). The changes in tissue thickness at 1 and 5 years in the BRA group amounted to -0.28 and -0.66 mm at 1 mm, -0.21 and -0.46 mm at 3 mm, and -0.32 and -0.45 mm at 5 mm, respectively. The changes in the STM group amounted to -0.15 and -0.54 mm at 1 mm, -0.24 and -0.48 mm at 3 mm, and -0.32 and -0.57 mm at 5 mm, respectively. No significantly different medians were observed. CONCLUSIONS: Minimal profilometric and linear changes occurred at implant sites between baseline and 5 years, between implant and tooth sites and between the two implant systems.

Fresh frozen plasma: red blood cells (1:2) coagulation effect is equivalent to 1:1 and whole blood.

BACKGROUND: Preemptive treatment of trauma-associated coagulopathy involves transfusion of fresh frozen plasma (FFP) at 1:1 ratio with red blood cells (RBCs), but the optimal ratio remains controversial. In combat theaters, fresh whole blood (FWB) is also an option. The objective of this study was to determine the effect of FFP:RBC ratios 1:1, 1:2, 1:3 and FWB on coagulation during resuscitation. MATERIALS AND METHODS: Thirty-six rats were randomized in the following six groups: Group 1: sham; Group 2: hemorrhage followed by sole lactated Ringer (LR) infusion; Group 3: FFP:RBC (1:1); Group 4: FFP:RBC (1:2); Group 5: FFP:RBC (1:3); Group 6: FWB transfusion. Another 25 animals were used for blood harvesting. Hemorrhage was induced by withdrawing 40% of total blood volume, mean arterial pressure (MAP) decreased to 45% of baseline, and laparotomy. Animals underwent LR infusion followed by blood product transfusion preset for each group. Blood samples were obtained at baseline and in the 105th minute for thromboelastometry and lactate. RESULTS: Hemorrhage caused a significant decrease in MAP and increase in lactate (P < 0.05). MAP was persistently low in group 2 despite fluid infusion (P < 0.05), but not in the other groups after 20 min of resuscitation. Mean clot formation time, alpha angle, and maximum clot firmness decreased significantly (P < 0.05) in group 2 (LR) and group 5 (1:3) compared with other groups. CONCLUSIONS: FFP:RBC in a 1:2 ratio optimally harnessed hemostatic resuscitation and prudent use of blood products compared with 1:1 and 1:3 ratios and to FWB transfusion.

Sensing in the collaborative Internet of Things.

We are entering a new era of computing technology, the era of Internet of Things (IoT). An important element for this popularization is the large use of off-the-shelf sensors. Most of those sensors will be deployed by different owners, generally common users, creating what we call the Collaborative IoT. This collaborative IoT helps to increase considerably the amount and availability of collected data for different purposes, creating new interesting opportunities, but also several challenges. For example, it is very challenging to search for and select a desired sensor or a group of sensors when there is no description about the provided sensed data or when it is imprecise. Given that, in this work we characterize the properties of the sensed data in the Internet of Things, mainly the sensed data contributed by several sources, including sensors from common users. We conclude that, in order to safely use data available in the IoT, we need a filtering process to increase the data reliability. In this direction, we propose a new simple and powerful approach that helps to select reliable sensors. We tested our method for different types of sensed data, and the results reveal the effectiveness in the correct selection of sensor data.

Electrospun nonwoven fabric of poly(ε-caprolactone)/n-phosphonium chitosan for antiviral applications: Fabrication, characterization, and potential efficacy.

This work reports the virucidal properties of nonwoven fibers developed via electrospinning with polycaprolactone (PCL) and chitosan quaternized with phosphonium salt (NPCS), emphasizing the influence of NPCS concentration on the structure of fibers and their performance against the MHV-3 coronavirus. The addition of NPCS enhances solutions conductivity and viscosity, leading to fibers containing a finer porous structure with a more hydrophilic and smoother surface, thereby making them a potent barrier against respiratory particles, which is a key factor for protective face masks. In terms of degradation, NPCS paced-up the process, suggesting potential environmental benefits. PCL/NPCS (90/10) fibers exhibit a 99 % coronavirus inhibition within a five-minute exposure without cellular toxicity, while also meeting breathability standards for medical masks. These findings suggest the use of NPCS as a promising strategy to design materials with remarkable virucidal performance and physical characteristics that reinforce their use in the field of biomaterials engineering.

Early placement of a non-invasive, pressure-regulated, fascial reapproximation device improves reduction of the fascial gap in open abdomens: a retrospective cohort study.

Background: Since current fascial traction methods involve invasive procedures, they are generally employed late in the management of the open abdomen (OA). This study aimed to evaluate early versus late placement of a non-invasive, pressure-regulated device for fascial reapproximation and gap reduction in OA patients. Methods: The study included all patients who had the abdominal fascia intentionally left open after damage control operation for trauma and emergency general surgery and were managed with the device in an academic hospital between January 1, 2020, and December 31, 2023. Time of device placement in relation to the end of index laparotomy was defined as early (≤24 hours) versus late (>24 hours). Time-related mid-incisional width reduction of the fascial gap and fascial closure were assessed using descriptive and linear regression analysis. Results: There was a significantly higher percent reduction in the fascial gap at the midpoint of the laparotomies in the early (≤24 hours) AbClo placement group compared with the late (>24 hours) AbClo placement group, respectively, median 76% versus 43%, p<0.001. Linear regression adjusting for body mass index and the number of takebacks indicated that fascial approximation was 22% higher for early placement (ß=0.22; CI 0.12, 0.33, p<0.001). Primary myofascial closure rate with early (≤24 hours) application of the device was 98% versus 85% with late application. Conclusion: Early non-invasive application of the device (≤24 hours) after the initial laparotomy resulted in greater reduction of the fascial gap and higher primary fascial closure rate compared with late placement (>24 hours). Early non-invasive intervention could prevent abdominal wall myofascial retraction in OA patients. Level of evidence: IV.

Antimicrobial activity of hydralazine against methicillin-resistant and methicillin-susceptible Staphylococcus aureus.

Background: Staphylococcus aureus is a human pathogen responsible for high mortality rates. The development of new antimicrobials is urgent. Materials & methods: The authors evaluated the activity of hydralazine along with its synergism with other drugs and action on biofilms. With regard to action mechanisms, the authors evaluated cell viability, DNA damage and molecular docking. Results: MIC and minimum bactericidal concentration values ranged from 128 to 2048 µg/ml. There was synergism with oxacillin (50%) and vancomycin (25%). Hydralazine reduced the viability of biofilms by 50%. After exposure to hydralazine 2× MIC, 58.78% of the cells were unviable, 62.07% were TUNEL positive and 27.03% presented damage in the comet assay (p < 0.05). Hydralazine showed affinity for DNA gyrase and TyrRS. Conclusion: Hydralazine is a potential antibacterial.

Staphylococcus aureus is a bacterium that can cause infection. Infections of S. aureus are becoming difficult to treat, but developing new drugs is a challenge. Repurposing them may be easier. This study looks at the possibility of using hydralazine, a type of medicine used to treat high blood pressure, against S. aureus. The authors found that hydralazine can kill S. aureus and can be used with other antibiotics, including oxacillin and vancomycin. Hydralazine interferes with important processes for the multiplication and survival of this bacterium. These results are preliminary but encouraging. Further studies are needed to confirm the use of hydralazine as a new treatment for S. aureus infections.

Circulating Tumor Cells Adhesion: Application in Biosensors.

The early and non-invasive diagnosis of tumor diseases has been widely investigated by the scientific community focusing on the development of sensors/biomarkers that act as a way of recognizing the adhesion of circulating tumor cells (CTCs). As a challenge in this area, strategies for CTCs capture and enrichment currently require improvements in the sensors/biomarker's selectivity. This can be achieved by understanding the biological recognition factors for different cancer cell lines and also by understanding the interaction between surface parameters and the affinity between macromolecules and the cell surface. To overcome some of these concerns, electrochemical sensors have been used as precise, fast-response, and low-cost transduction platforms for application in cytosensors. Additionally, distinct materials, geometries, and technologies have been investigated to improve the sensitivity and specificity properties of the support electrode that will transform biochemical events into electrical signals. This review identifies novel approaches regarding the application of different specific biomarkers (CD44, Integrins, and EpCAm) for capturing CTCs. These biomarkers can be applied in electrochemical biosensors as a cytodetection strategy for diagnosis of cancerous diseases.

Antifungal activity of cisatracurium against fluconazole-resistant Candida isolates and its antibiofilm effects.

Aim: To evaluate the antifungal activity of cisatracurium against Candida spp. resistant to fluconazole strains in planktonic and biofilm forms, in addition to determining its mechanism of action. Materials & methods: Antifungal activity and pharmacological interactions were determined using broth microdilution methods and the mechanism of action was evaluated by flow cytometry and molecular docking. Results: Cisatracurium presented antifungal activity against Candida spp. planktonic cells due to alterations of mitochondrial transmembrane potential leading to cellular apoptosis in addition to interacting with important targets related to cellular respiration, membrane and cell wall evidenced by molecular docking. Furthermore, the drug both prevented biofilm formation and impaired mature biofilms. Conclusion: Cisatracurium exhibits potential antifungal activity against Candida spp.

Synergistic effect of hydralazine associated with triazoles on Candida spp. in planktonic cells.

Objective: To evaluate the antifungal activity of hydralazine hydrochloride alone and in synergy with azoles against Candida spp. and the action mechanism. Methods: We used broth microdilution assays to determine the MIC, checkerboard assays to investigate synergism, and flow cytometry and molecular docking tests to ascertain action mechanism. Results: Hydralazine alone had antifungal activity in the range of 16-128 µg/ml and synergistic effect with itraconazole versus 100% of the fungal isolates, while there was synergy with fluconazole against 11.11% of the isolates. There was molecular interaction with the receptors exo-B(1,3)-glucanase and CYP51, causing reduced cell viability and DNA damage. Conclusion: Hydralazine is synergistic with itraconazole and triggers cell death of Candida spp. at low concentrations, demonstrating antifungal potential.

Predictors of initial management failure in traumatic hemothorax: A prospective multicenter cohort analysis.

BACKGROUND: Traumatic hemothorax is common, and management failure leads to worse outcomes. We sought to determine predictive factors and understand the role of trauma center performance in hemothorax management failure. METHODS: We prospectively examined initial hemothorax management (observation, pleural drainage, surgery) and failure requiring secondary intervention in 17 trauma centers. We defined hemothorax management failure requiring secondary intervention as thrombolytic administration, tube thoracostomy, image-guided drainage, or surgery after failure of the initial management strategy at the discretion of the treating trauma surgeon. Patient-level predictors of hemothorax management failure requiring secondary intervention were identified for 2 subgroups: initial observation and immediate pleural drainage. Trauma centers were divided into quartiles by hemothorax management failure requiring secondary intervention rate and hierarchical logistic regression quantified variation. RESULTS: Of 995 hemothoraces in 967 patients, 186 (19%) developed hemothorax management failure requiring secondary intervention. The frequency of hemothorax management failure requiring secondary intervention increased from observation to pleural drainage to surgical intervention (12%, 22%, and 35%, respectively). The number of ribs fractured (odds ratio 1.12 per fracture; 95% confidence interval 1.00-1.26) and pulmonary contusion (odds ratio 2.25, 95% confidence interval 1.03-4.91) predicted hemothorax management failure requiring secondary intervention in the observation subgroup, whereas chest injury severity (odds ratio 1.58; 95% confidence interval 1.17-2.12) and initial hemothorax volume evacuated (odds ratio 1.10 per 100 mL; 95% confidence interval 1.05-1.16) predicted hemothorax management failure requiring secondary intervention after pleural drainage. After adjusting for patient characteristics in the logistic regression model for hemothorax management failure requiring secondary intervention, patients treated at high hemothorax management failure requiring secondary intervention trauma centers were 6 times more likely to undergo an intervention after initial hemothorax management failure than patients treated in low hemothorax management failure requiring secondary intervention trauma centers (odds ratio 6.18, 95% confidence interval 3.41-11.21). CONCLUSION: Failure of initial management of traumatic hemothorax is common and highly variable across trauma centers. Assessing patient selection for a given management strategy and center-level practices represent opportunities to improve outcomes from traumatic hemothorax.

Three-Dimensional Printing and Its Potential to Develop Sensors for Cancer with Improved Performance.

Cancer is the second leading cause of death globally and early diagnosis is the best strategy to reduce mortality risk. Biosensors to detect cancer biomarkers are based on various principles of detection, including electrochemical, optical, electrical, and mechanical measurements. Despite the advances in the identification of biomarkers and the conventional 2D manufacturing processes, detection methods for cancers still require improvements in terms of selectivity and sensitivity, especially for point-of-care diagnosis. Three-dimensional printing may offer the features to produce complex geometries in the design of high-precision, low-cost sensors. Three-dimensional printing, also known as additive manufacturing, allows for the production of sensitive, user-friendly, and semi-automated sensors, whose composition, geometry, and functionality can be controlled. This paper reviews the recent use of 3D printing in biosensors for cancer diagnosis, highlighting the main advantages and advances achieved with this technology. Additionally, the challenges in 3D printing technology for the mass production of high-performance biosensors for cancer diagnosis are addressed.

The natural history of trauma-related coagulopathy: implications for treatment.

BACKGROUND: Hemorrhage is a leading cause of death in trauma patients and coagulopathy is a significant contributor. Although the exact mechanisms of trauma-associated coagulopathy (TAC) are incompletely understood, hemostatic resuscitation strategies have been developed to treat TAC. Our study sought to identify which trauma patients develop TAC and the factors associated with its development, to describe the natural history of TAC, and to identify patients with TAC who may not require hemostatic resuscitation. METHODS: Patients with early coagulopathy (International Normalized Ratio >1.3) who were admitted directly from the scene within 1 hour of injury were identified in our institutional trauma registry. We analyzed these data for the presence of TAC, predictors of early and delayed TAC, and evolution of TAC during the first 24 hours of admission. RESULTS: Of 2,473 patients, 290 (12%) had early TAC (International Normalized Ratio >1.3) and 271 (11%) developed delayed TAC. Multivariate analysis identified female gender (odds ratio [OR] 1.25 [1.11-1.41]), lower pH (OR 0.08 [0.015-0.47]), lower hemoglobin (OR 0.96 [0.95-0.97]), lower temperature (OR 0.82 [0.70-0.95]), and blunt mechanism (OR 0.49 [0.33-0.71]) as factors significantly associated with development of early TAC. Progression of early TAC occurred in 64%, and these patients had more severe abdominal injury and received more emergency room crystalloid. Of patients with early TAC who did not receive fresh frozen plasma, only 49% developed worsening coagulopathy. Patients with isolated intracranial hemorrhage had higher rates of bleeding progression (75% vs. 20%, p < 0.005) in the presence of early TAC. CONCLUSIONS: TAC may appear in an early or delayed form and its presence and progression are associated with a number of identifiable factors. Although TAC commonly progresses, it also resolves spontaneously in many patients. Further research is required to identify which patients with TAC require hemostatic treatment, although those with intracranial hemorrhages seem to warrant aggressive therapy.

Evaluation of the antifungal activity in vitro of midazolam against fluconazole-resistant Candida spp. isolates.

Aim: The purpose of this study was to evaluate the antifungal activity of midazolam, alone and in association with azoles, against isolates of clinical Candida spp. in planktonic and biofilm form. Materials & methods: The antifungal activity was observed using the broth microdilution technique. Flow cytometry tests were performed to investigate the probable mechanism of action and the comet test and cytotoxicity test were applied to evaluate DNA damage. Results: Midazolam (MIDAZ) showed antifungal activity against planktonic cells (125-250 µg/ml) and reduced the viability of Candida spp. biofilms (125 a 2500 µg/ml). The interaction of MIDAZ against Candida spp. biofilms was observed through scanning electron microscopy, causing alteration of their appearance. Therefore, MIDAZ has antifungal potential against Candida spp.

Synergistic activity of diclofenac sodium with oxacillin against planktonic cells and biofilm of methicillin-resistant Staphylococcus aureus strains.

Aim: To evaluate the activity of diclofenac sodium and synergism with oxacillin against clinical strains of SARM in plactonic cells, antibiofilm and biofilm. Materials & methods: Synergism activity was assessed using the fractional inhibitory concentration index and its possible mechanism of action by flow cytometry. Results: The synergistic activity of diclofenac sodium with oxacillin was observed against plactonic cells, antibiofilm and in biofilm formed from clinical methicillin-resistant Staphylococcus aureus strains. Conclusion: This combination caused damage to the integrity of the membrane and ruptures in the DNA of the cells, leading to apoptosis.