Is Subcapital Realignment for Slipped Capital Femoral Epiphysis a Reproducible Technique? Midterm Results.

BACKGROUND: The modified Dunn procedure, which is based on the development of an extended retinacular flap containing the blood supply for the femoral head, allows anatomic reestablishment in patients with moderate to severe slipped capital femoral epiphysis (SCFE). Some controversy exists regarding the short-term to midterm risk of avascular necrosis (AVN) and other complications resulting from the surgical technique. QUESTIONS/PURPOSES: (1) What percentage of patients treated with an extended retinacular flap during the modified Dunn procedure for SCFE with a moderate (slip angle from 30° to 60°) or severe slip (slip angle equal or greater than 60°) develop symptomatic AVN, and what percentage underwent further surgery or had other complications? (2) What femoral head-neck alignment and position parameters relative to the greater trochanter are achieved after surgery? (3) Can we identify radiographic signs of osteoarthritis at a minimum of 4 years after surgery? METHODS: Between January 2006 and December 2018, we treated 61 patients for SCFE. During this time, we generally used the modified Dunn procedure when the slip angle was ≥ 30°. Based on this indication, the modified Dunn procedure was performed in 37 patients (41 hips) during that time period, and those patients were potentially eligible for this retrospective study. Because bilateral hips in the same patient are not statistically independent, for our analyses, we analyzed only the hip with the longer follow-up time. Of those who remained, 11% (4) were lost before the minimum study follow-up of 48 months or had incomplete datasets, leaving 89% (33) for analysis here at a median follow-up of 80 months (range 49 to 208 months). Periacetabular osteotomy or subtrochanteric rotational femoral osteotomy was added under the same anaesthesia time in 33% (11 patients). We added periacetabular osteotomy in 24% (8) when intraoperative anterior instability was present in external rotation. A femoral rotational osteotomy was added in 9% (3) when posterior instability was present in flexion and internal rotation. The mean ± standard deviation age at the time of surgery was 13 ± 1 years, and 33% (11 of 33) of patients were female. The mean slip angle was 51° ± 16º, and 15% (5) of hips had unstable slips, defined as an inability to walk with or without crutches. We documented chronic presentations in 82% (27) of patients, acute and chronic in 12% (4), and acute in 6% (2). The rate of symptomatic AVN was determined by reviewing all radiographs obtained at the latest follow-up interval. Further surgery and other complications were assessed through an electronic medical record review. Radiographic morphologic parameters were measured before surgery and at a minimum follow-up of 4 years by two senior orthopaedic surgeons. Radiographs obtained at the latest follow-up visit were also screened for signs of osteoarthritis by the same surgeons. RESULTS: At the latest follow-up, 3% (1 patient) of patients developed symptomatic AVN and underwent further surgery and 3% (1) underwent revision surgery for screw breakage after a high-energy fall. Postoperatively, the alpha angle was restored to 39º ± 6º, the anterior head-neck offset was restored to 8 ± 3 mm, the neck-shaft angle was 136º ± 6º, and the presence of a positive Klein line decreased from 64% (21 hips) to 0% (0 hips). No patients showed radiographic signs of osteoarthritis at the minimum follow-up of 4 years. CONCLUSION: In this series, the modified Dunn procedure in moderate and severe slips was a reproducible procedure, and few patients developed symptomatic AVN or experienced other complications. Hip morphology was restored, but a longer follow-up duration and a detailed analysis of the results from other centers is warranted to assess the possible long-term risk of progression to AVN or osteoarthritis. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Doxycycline reduces liver and kidney injuries in a rat hemorrhagic shock model.

BACKGROUND: Hemorrhagic shock (HS), which causes insufficient tissue perfusion, can result in multiple organ failure (MOF) and death. This study aimed to evaluate whether doxycycline (DOX) protects cardiovascular, kidney, and liver tissue from damage in a rat model of HS. Immediately before the resuscitation, DOX (10 mg/kg; i.v.) was administered, and its protective effects were assessed 24 h later. Mean arterial pressure, renal blood flow, heart rate, vasoactive drug response, and blood markers such as urea, creatinine, AST, ALT, CPK, CPR, and NOx levels were determined. RESULTS: We showed that DOX has a significant effect on renal blood flow and on urea, creatinine, AST, ALT, CPK, and NOx. Morphologically, DOX reduced the inflammatory process in the liver tissue. CONCLUSIONS: We conclude that DOX protects the liver and kidney against injury and dysfunction in a HS model and could be a strategy to reduce organ damage associated with ischemia-and-reperfusion injury.

Diversity and botanical composition of native species in the Pampa biome in vineyards cultivated on soils with high levels of copper, zinc and manganese and phytoremediation potential.

Viticulture allows the preservation of native species inside vineyards in the Pampa biome. However, phytosanitary treatments in these areas can increase the levels of Cu, Zn and Mn. The study aimed to (i) verify the influence of Cu, Zn and Mn contents in Pampa biome soils; (ii) identify variables related to Cu, Zn and Mn that most contribute to the variation in richness, diversity, and dry matter production of native vegetation, (iii) investigate the phytoremediation potential of species present in vineyards. Botanical composition, Cu, Zn, Mn available in the soil, and plant nutritional composition in two vineyards (V1 and V2) and native field (NF) were evaluated. Vineyards showed higher Cu, Zn and Mn contents in the soil, resulting in the lowest biomass, richness, and diversity of native species. Mn in tissue was the most important variable in explaining the variation in dry matter. Zn in the soil helped to explain the difference in species richness and diversity. P concentration in tissue was important in elucidating the variation in species diversity. Paspalum plicatulum and Paspalum notatum have potential for phytostabilization of metals in vineyards.

On the Structural, Thermal, Micromechanical and Tribological Characterizations of Cu-Filled Acrylonitrile Butadiene Styrene Micro-Composites.

The purpose of this work was to investigate the structural, thermal, micromechanical and tribological properties of novel polymer/metal composite materials for bearing applications. Copper (Cu)-filled Acrylonitrile Butadiene Styrene (ABS) composites were mixed in a laboratory scale by an internal mixer with two blade impellers, and then injection-molded. Neat ABS, ABS+5wt% Cu, ABS+10wt% Cu, and ABS+15wt% Cu were the four materials that were tested. The dispersion of Cu particles in the ABS matrix was investigated using Scanning Electron Microscopy (SEM) and a micro-tomography scan. The filler particles have a uniform distribution in the matrix, according to the observations. The incorporation of Cu filler also refined an increase in the glass transition temperature from Differential Scanning Calorimetry (DSC) and less intensity in the amorphous phase by X-ray diffraction (XRD). Nanoindentation tests were carried out to characterize the micro-mechanical behavior of the composites. Friction and wear analysis were also examined using a pin-on-disk tribometer. Compared with neat ABS, all the micro-composites showed much higher indentation hardness, Vickers hardness, and indentation elastic modulus. It was also concluded that the incorporation of Cu filler into ABS simultaneously improved the friction and wear properties of the composites, which contributed to the suitability of the micro-filled composites with hard metallic particles for a wider range of mechanical components for bearing applications.

Cannabinoid CB2 receptor agonist reduces local and systemic inflammation associated with pneumonia-induced sepsis in mice.

Sepsis is a severe condition secondary to dysregulated host response to infection leading to tissue damage and organ dysfunction. Cannabinoid CB2 receptor has modulatory effects on the immune response. Therefore, this study investigated the effects of a cannabinoid CB2 receptor agonist on the local and systemic inflammatory process associated with pneumonia-induced sepsis. Pneumonia-induced sepsis was induced in mice by intratracheal inoculation of Klebsiella pneumoniae. Tissue and bronchoalveolar lavage (BAL) were collected 6, 24, or 48 h after surgery. Mice were treated with CB2 agonist (AM1241, 0.3 and 3 mg/kg, i.p.) and several parameters of inflammation were evaluated 24 h after sepsis induction. Polymorphonuclear cell migration to the infectious focus peaked 24 h after pneumonia-induced sepsis induction in male and female animals. Septic male mice presented a significant reduction of cannabinoid CB2 receptor density in the lung tissue after 24 h, which was not observed in females. CB2 expression in BAL macrophages was also reduced in septic animals. Treatment of septic mice with AM1241 reduced cell migration, local infection, myeloperoxidase activity, protein extravasation, and NOS-2 expression in the lungs. In addition, the treatment reduced plasma IL-1ß, increased IL-10 and reduced the severity and mortality of septic animals. These results suggest that AM1241 promotes an interesting balance in the inflammatory response, maintaining lung function and preventing organ injury. Therefore, cannabinoid CB2 receptors are potential targets to control the excessive inflammatory process that occurs in severe conditions, and agonists of these receptors can be considered promising adjuvants in pneumonia-induced sepsis treatment.

Assessment of the Risk Factors Related to the Length of Hospital Stay and Postoperative Complications in Patients Undergoing Primary Total Knee Arthroplasty.

Objective To assess the risk factors involving longer hospital stays and early postoperative complications (first 30 days after surgery) in patients undergoing total knee arthroplasty (TKA). Materials and Methods A cross-sectional study was conducted with collection of data of patients who underwent TKA in a private hospital between 2015 and 2019. The following data were collected: age, gender, body mass index, and clinical comorbidities. We also collected intraoperative data such as the grade on the classification of the American Society of Anesthesiologists (ASA), the duration of the surgery, the length of stay, the postoperative complications, and readmission within 30 days. Statistical models were used to investigate the possible risk factors associated with longer hospital stays and postoperative complications. Results There was evidence of an increase in the length of hospital stay in older patients, with higher grades on the ASA classification or who suffered postoperative complications. For each increase in 1 year of age, we expect the length of stay to be multiplied by 1.008 (95% confidence interval [95%CI]: 1.004 to 1.012; p < 0,001). In patients who were ASA grade III, the time is expected to be multiplied by 1.297 (95%CI: 1.083 to 1.554; p = 0,005) when compared with grade-I patients. In patients who suffered postoperative complications, the time is expected to be multiplied by 1.505 (95%CI: 1.332 to 1.700; p < 0.001) compared with patients without complications. Conclusion The present study demonstrated that, in patients who underwent primary TKA, preoperative characteristics such as older age and ASA grade ≥ III, as well as the development of postoperative complications, independently predict the increase in the length of hospital stay.

Hydrophobic DES Based on Menthol and Natural Organic Acids for Use in Antifouling Marine Coatings.

Marine biofouling negatively impacts industries with off-shore infrastructures, such as naval, oil, and aquaculture. To date, there are no ideal sustainable, economic, and environmentally benign solutions to deal with this phenomenon. The advances achieved in green solvents, as well as its application in different industries, such as pharmaceutical and biotechnology, have promoted the emergence of deep eutectic systems (DES). These eutectic systems have applications in various fields and can be revolutionary in the marine-based industrial sector. In this study, the main objective was to investigate the potential use of hydrophobic DES (HDES) based on menthol and natural organic acids for their use as marine antifouling coatings. Our strategy encompassed the physicochemical characterization of different formulations, which allowed us to identify the most appropriate molar ratio and intermolecular interactions for HDES formations. The miscibility of the resulting HDES with the marine coating has been evaluated and proven to be successful. The Men/OL (1:1) system proved to be the most promising in terms of cost-production and thus was the one used in subsequent antifouling tests. The cytotoxicity of this HDES was evaluated using an in vitro cell model (HaCat cells) showing no significant toxicity. Furthermore, the application of this system incorporated into coatings that are used in marine structures was also studied using marine species (Mytilus edulis mussels and Patella vulgata limpets) to evaluate both their antifouling and ecotoxicity effects. HDES Men/OL (1:1) incorporated in marine coatings was promising in reducing marine macrofouling and also proved to be effective at the level of microfouling without viability impairment of the tested marine species. It was revealed to be more efficient than using copper oxide, metallic copper, or ivermectin as antifouling agents. Biochemical assays performed on marine species showed that this HDES does not induce oxidative stress in the tested species. These results are a strong indication of the potential of this HDES to be sustainable and efficiently used in marine fouling control technologies.

Alginate-Chitosan Membranes for the Encapsulation of Lavender Essential Oil and Development of Biomedical Applications Related to Wound Healing.

Biopolymers such as chitosan (CHT) or alginate (ALG) are among the most prominent for health-related applications due to their broad bioactivity. Their combination for the preparation of membranes is hereby proposed as an application for wound healing with the incorporation of lavender essential oil (LEO), widely known for its antioxidant and antimicrobial properties. The preparation of CHT, CHT + LEO, ALG, ALG + LEO, and CHT/ALG + LEO membranes was accomplished, and its composition was analyzed using Fourier Transform Infrared Spectroscopy (FTIR). The water absorption capacity and oil release profile of the membranes revealed higher water uptake capacity when a lower LEO release was obtained. The combined CHT/ALG + LEO film showed a water uptake percentage of 638% after 48 h and a maximum LEO release concentration of 42 mg/L. Cytotoxicity and biocompatibility of the prepared membranes were studied using a HaCaT cell line, with an assessment of cell viability regarding film leachables, DNA quantification, and DAPI-phalloidin staining. The results revealed that the indirect contact of the prepared membranes via its leachables does not compromise cell viability, and upon direct contact, cells do not adhere or proliferate on the surface of the membranes. Moreover, the CHT/ALG + LEO membrane increases cell proliferation, making it suitable for applications in wound healing.

Assessment of the Risk Factors Related to the Length of Hospital Stay and Postoperative Complications in Patients Undergoing Primary Total Knee Arthroplasty / Avaliação dos fatores de risco relacionados ao tempo de internação e às complicações pós-operatórias em pacientes submetidos a artroplastia total primária do joelho

Abstract Objective To assess the risk factors involving longer hospital stays and early postoperative complications (first 30 days after surgery) in patients undergoing total knee arthroplasty (TKA). Materials and Methods Across-sectional study was conducted with collection of data of patients who underwent TKA in a private hospital between 2015 and 2019. The following data were collected: age, gender, body mass index, and clinical comorbid-ities. We also collected intraoperative data such as the grade on the classification of the American Society of Anesthesiologists (ASA), the duration of the surgery, the length of stay, the postoperative complications, and readmission within 30 days. Statistical models were used to investigate the possible risk factors associated with longer hospital stays and postoperative complications. Results There was evidence of an increase in the length of hospital stay in older patients, with higher grades on the ASA classification or who suffered postoperative complications. For each increase in 1 year of age, we expect the length of stay to be multiplied by 1.008 (95% confidence interval [95%CI]: 1.004 to 1.012; p < 0,001). In patients who were ASA grade III, the time is expected to be multiplied by 1.297 (95%CI: 1.083 to 1.554; p = 0,005) when compared with grade-I patients. In patients who suffered postoperative complications, the time is expected to be multiplied by 1.505 (95%CI: 1.332 to 1.700; p < 0.001) compared with patients without complications. Conclusion The present study demonstrated that, in patients who underwent primary TKA, preoperative characteristics such as older age and ASA grade > III, as well as the development of postoperative complications, independently predict the increase in the length of hospital stay.

Resumo Objetivo Avaliar os fatores de risco relacionados a um tempo de internação mais longo e às complicações pós-operatórias precoces (primeiros 30 dias após a cirurgia) em pacientes submetidos a artroplastia total do joelho (ATJ). Materiais e Métodos Este é um estudo transversal com coleta de dados de pacientes submetidos a ATJ em um hospital privado entre 2015 e 2019. Os seguintes dados foram coletados: idade, gênero, índice de massa corporal, e comorbidades clínicas. Também coletamos dados intraoperatórios, como o grau na classificação da American Society of Anesthesiologists (ASA) e a duração da cirurgia, além do tempo de internação, as complicações pós-operatórias, e a readmissão em 30 dias. Os possíveis fatores de risco associados a um tempo de internação mais longo e às taxas de complicações pós-operatórias foram investigados por meio de modelos estatísticos. Resultados Os pacientes mais velhos, com graus mais elevados na classificação da ASA ou que sofreram complicações pós-operatórias, ficaram internados por mais tempo. Para cada aumento em um ano de idade, esperamos que o tempo de internação seja multiplicado por 1,008 (intervalo de confiança de 95% [IC95%]: 1,004 a 1,012; p < 0,001). Em pacientes de grau III na classificação da ASA, espera-se que o tempo seja multiplicado por 1,297 (IC95%: 1,083 a 1,554; p = 0,005) em comparação com pacientes de grau I. Em pacientes com complicações pós-operatórias, espera-se que o tempo seja multiplicado por 1,505 (IC95%: 1,332 a 1,700; p < 0,001) em comparação com pacientes sem complicações. Conclusão Este estudo demonstrou que, em pacientes submetidos a ATJ primária, características pré-operatórias, como idade avançada e grau ≥ III na classificação da ASA, e o desenvolvimento de complicações pós-operatórias predizem o aumento do tempo de internação hospitalar de forma independente.

Bioactivity Enhancement of Plasma-Sprayed Hydroxyapatite Coatings through Non-Contact Corona Electrical Charging.

Atmospheric plasma spray (APS) remains the only certified industrial process to produce hydroxyapatite (Hap) coatings on orthopaedic and dental implants intended for commercialization. Despite the established clinical success of Hap-coated implants, such as hip and knee arthroplasties, a concern is being raised regarding the failure and revision rates in younger patients, which are increasing rapidly worldwide. The lifetime risk of replacement for patients in the 50-60 age interval is about 35%, which is significantly higher than 5% for patients aged 70 or older. Improved implants targeted at younger patients are a necessity that experts have been alerted to. One approach is to enhance their bioactivity. For this purpose, the method with the most outstanding biological results is the electrical polarization of Hap, which remarkably accelerates implant osteointegration. There is, however, the technical challenge of charging the coatings. Although this is straightforward on bulk samples with planar faces, it is not easy on coatings, and there are several problems regarding the application of electrodes. To the best of our knowledge, this study demonstrates, for the first time, the electrical charging of APS Hap coatings using a non-contact, electrode-free method: corona charging. Bioactivity enhancement is observed, establishing the promising potential of corona charging in orthopedics and dental implantology. It is found that the coatings can store charge at the surface and bulk levels up to high surface potentials (>1000 V). The biological in vitro results show higher Ca2+ and P5+ intakes in charged coatings compared to non-charged coatings. Moreover, a higher osteoblastic cellular proliferation is promoted in the charged coatings, indicating the promising potential of corona-charged coatings when applied in orthopedics and dental implantology.

Menthol-based deep eutectic systems as antimicrobial and anti-inflammatory agents for wound healing.

Effective antimicrobial treatment has been identified as a serious and unmet medical need. Herein, we present a strategy based on deep eutectic systems (DES) to overcome current limitations, answering the need not only to effectively kill bacterial agents but also to avoid their adhesion and proliferation, which is associated with biofilm formation and have a crucial impact on bacterial virulence. To achieve such a goal, natural deep eutectic systems (NADES) based on menthol (Me) and saturated free fatty acids (FFA) were produced, fully physicochemical characterized, and its bioactive properties were described. The antimicrobial potential of menthol-based NADES with FFA, namely, myristic acid (MA), lauric acid (LA), and stearic acid (SA) were investigated towards a broad panel of microorganisms. The obtained data indicates that NADES possess effective antimicrobial properties towards the Gram-positive bacterial and fungal strains tested. Among the tested formulations, Me:LA at a molar ratio of 4:1 molar was used to carry out a biofilm detachment/removal assay due to is superior microbiological properties. This formulation was able to effectively lead to biofilm removal/dispersion of not only methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans, but also Escherichia coli, without the need of any additional physical force or antibiotic. Furthermore, since microbial invasion and biofilm formation is highly undesired in wound healing, namely in chronic wound healing, the wound healing properties of these eutectic formulations was also investigated. The results suggest that these NADES can cope with microbial invasion and biofilm detachment while not compromising normal keratinocyte proliferation and migration verified in wound healing and epidermis repair, while also contributing to the reduction of cell stress and inflammation via the control of ROS production. In conclusion, these results provide the indication that NADES based on Me and FFA holds great interest as antimicrobial agents for preventive and therapeutic applications in various clinical settings, including wound healing.

Inhibition of Bruton's Tyrosine Kinase Activity Attenuates Hemorrhagic Shock-Induced Multiple Organ Dysfunction in Rats.

OBJECTIVE: The aim of this study was to investigate (a) the potential of the Bruton's tyrosine kinase (BTK) inhibitors acalabrutinib and fenebrutinib to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) hemorrhagic shock (HS) rat models and (b) whether treatment with either acalabrutinib or fenebrutinib attenuates BTK, NF-κB and NLRP3 activation in HS. BACKGROUND: The MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. The protein BTK is known to play a role in the activation of the NLRP3 inflammasome, which is a key component of the innate inflammatory response. However, its role in trauma-hemorrhage is unknown. METHODS: Acute HS rat models were performed to determine the influence of acalabrutinib or fenebrutinib on MODS. The activation of BTK, NF-κB and NLRP3 pathways were analyzed by western blot in the kidney. RESULTS: We demonstrated that (a) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (b) treatment of HS-rats with either acalabrutinib or fenebrutinib attenuated the organ injury and dysfunction in acute HS models and (c) reduced the activation of BTK, NF- kB and NLRP3 pathways in the kidney. CONCLUSION: Our results point to a role of BTK in the pathophysiology of organ injury and dysfunction caused by trauma/hemorrhage and indicate that BTK inhibitors may be repurposed as a potential therapeutic approach for MODS after trauma and/or hemorrhage.

Microbial Contamination in the Coffee Industry: An Occupational Menace besides a Food Safety Concern?

Respiratory abnormalities among workers at coffee roasting and packaging facilities have already been reported; however, little is known about microbiological contamination inside coffee production facilities. This study intends to assess the microbial contamination (fungi and bacteria) in two coffee industries from Brazil with a multi-approach protocol for sampling and for subsequent analyses using four main sources of samples: filtering respiratory protection devices (FRPD) used by workers, settled dust, electrostatic dust cloths (EDC) and coffee beans. The fungal contamination in the assessed industries was also characterized through the molecular detection of toxigenic species and antifungal resistance. Total bacteria contamination presented the highest values in FRPD collected from both industries (7.45 × 104 CFU·m-2; 1.09 × 104 CFU·m-2). Aspergillus genera was widespread in all the environmental samples collected and sections with clinical relevance (Fumigati) and with toxigenic potential (Nigri and Circumdati) were recovered from FRPD. Circumdati section was observed in 4 mg/mL itraconazole. Sections Circumdati (EDC, coffee beans and settled dust) and Nidulantes (EDC, coffee beans and FRPD) were detected by qPCR. Some of the targeted Aspergillus sections that have been identified microscopically were not detected by qPCR and vice-versa. Overall, this study revealed that microbial contamination is a potential occupational risk in the milling stage and should be tackled when assessing exposure and performing risk assessment. In addition, a multi-sampling campaign should be the approach to follow when assessing microbial contamination and FRPD should be included in this campaign. Occupational exposure to mycotoxins should be considered due to high fungal diversity and contamination. A One Health approach should address these issues in order to prevent consumption of coffee crops and beans infected by fungi and, more specifically, to avoid widespread azole resistance.

Urban objects classification using Mueller matrix polarimetry and machine learning.

Detecting and recognizing different kinds of urban objects is an important problem, in particular, in autonomous driving. In this context, we studied the potential of Mueller matrix polarimetry for classifying a set of relevant real-world objects: vehicles, pedestrians, traffic signs, pavements, vegetation and tree trunks. We created a database with their experimental Mueller matrices measured at 1550 nm and trained two machine learning classifiers, support vector machine and artificial neural network, to classify new samples. The overall accuracy of over 95% achieved with this approach, with either models, reveals the potential of polarimetry, specially combined with other remote sensing techniques, to enhance object recognition.

Inflammation as a Prognostic Marker in Heart Failure.

BACKGROUND: Heart failure (HF) is a chronic cardiac disease of great importance worldwide and responsible for one-fifth of hospitalizations for cardiovascular disease in Brazil. Pro-inflammatory mediators are involved in the pathophysiology of HF. However, the impact of inflammatory markers on the prognosis of the disease remains uncertain. OBJECTIVE: We aimed to evaluate inflammation as a prognostic marker in chronic HF. METHODS: In this prospective, single-center, observational cohort study conducted from June 2018 through December 2019, we included outpatients with HF from a specialized service of a teaching hospital. Patients with decompensated HF requiring hospitalization in the last 30 days were excluded. At the time of inclusion, serum C-reactive protein (CRP) and albumin were collected and the presence of inflammation was defined as CRP/albumin ≥1.2. Patients with CRP/albumin ratio <1.2 (group A) and CRP/albumin ratio ≥1.2 (group B) were compared. The primary outcome was all-cause mortality. The secondary outcomes were hospitalization for decompensated HF, number of hospitalizations, and number of days of hospitalization in the 12-month follow-up. RESULTS: We included 77 patients, 49 (63.3%) in group A and 28 (3.4%) in group B. Six patients in group A (12.2%) and 10 patients in group B (35.7%) required at least one hospitalization during follow-up (p=0.01). The rate of hospitalizations for decompensated HF for every 100 patients was 16.3 in group A vs 50.0 in group B (p=0.0001) and the average in-hospital length of stay was 12.2 vs 14.2 days per hospitalized patient (p=0.36) in groups A and B, respectively. The mortality rate was 6.1% in group A vs 7.1% in group B (p=0.86). CONCLUSION: In HF outpatients with inflammation evidentiated by the CRP/albumin ratio ≥1.2, the risk of death was similar to patients without inflammation criteria. However, the presence of inflammation led to a three-fold higher risk of hospitalization for HF decompensation.

The role of nitric oxide in sepsis-associated kidney injury.

Sepsis is one of the leading causes of acute kidney injury (AKI), and several mechanisms including microcirculatory alterations, oxidative stress, and endothelial cell dysfunction are involved. Nitric oxide (NO) is one of the common elements to all these mechanisms. Although all three nitric oxide synthase (NOS) isoforms are constitutively expressed within the kidneys, they contribute in different ways to nitrergic signaling. While the endothelial (eNOS) and neuronal (nNOS) isoforms are likely to be the main sources of NO under basal conditions and participate in the regulation of renal hemodynamics, the inducible isoform (iNOS) is dramatically increased in conditions such as sepsis. The overexpression of iNOS in the renal cortex causes a shunting of blood to this region, with consequent medullary ischemia in sepsis. Differences in the vascular reactivity among different vascular beds may also help to explain renal failure in this condition. While most of the vessels present vasoplegia and do not respond to vasoconstrictors, renal microcirculation behaves differently from nonrenal vascular beds, displaying similar constrictor responses in control and septic conditions. The selective inhibition of iNOS, without affecting other isoforms, has been described as the ideal scenario. However, iNOS is also constitutively expressed in the kidneys and the NO produced by this isoform is important for immune defense. In this sense, instead of a direct iNOS inhibition, targeting the NO effectors such as guanylate cyclase, potassium channels, peroxynitrite, and S-nitrosothiols, may be a more interesting approach in sepsis-AKI and further investigation is warranted.

SUMOylation in peripheral tissues under low perfusion-related pathological states.

SUMOylation is described as a posttranslational protein modification (PTM) that is involved in the pathophysiological processes underlying several conditions related to ischemia- and reperfusion-induced damage. Increasing evidence suggests that, under low oxygen levels, SUMOylation might be part of an endogenous mechanism, which is triggered by injury to protect cells within the central nervous system. However, the role of ischemia-induced SUMOylation in the periphery is still unclear. This article summarizes the results of recent studies regarding SUMOylation profiles in several diseases characterized by impaired blood flow to the cardiorenal, gastrointestinal, and respiratory systems. Our review shows that although ischemic injury per se does not always increase SUMOylation levels, as seen in strokes, it seems that in most cases the positive modulation of protein SUMOylation after peripheral ischemia might be a protective mechanism. This complex relationship warrants further investigation, as the role of SUMOylation during hypoxic conditions differs from organ to organ and is still not fully elucidated.

Inhibition of Macrophage Migration Inhibitory Factor Activity Attenuates Haemorrhagic Shock-Induced Multiple Organ Dysfunction in Rats.

Objective: The aim of this study was to investigate (a) macrophage migration inhibitory factor (MIF) levels in polytrauma patients and rats after haemorrhagic shock (HS), (b) the potential of the MIF inhibitor ISO-1 to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) HS rat models and (c) whether treatment with ISO-1 attenuates NF-κB and NLRP3 activation in HS. Background: The MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. MIF is a pleiotropic cytokine which can modulate the inflammatory response, however, its role in trauma is unknown. Methods: The MIF levels in plasma of polytrauma patients and serum of rats with HS were measured by ELISA. Acute HS rat models were performed to determine the influence of ISO-1 on MODS. The activation of NF-κB and NLRP3 pathways were analysed by western blot in the kidney and liver. Results: We demonstrated that (a) MIF levels are increased in polytrauma patients on arrival to the emergency room and in rats after HS, (b) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (c) treatment of HS-rats with ISO-1 attenuated the organ injury and dysfunction in acute HS models and (d) reduced the activation of NF-κB and NLRP3 pathways in the kidney and liver. Conclusion: Our results point to a role of MIF in the pathophysiology of trauma-induced organ injury and dysfunction and indicate that MIF inhibitors may be used as a potential therapeutic approach for MODS after trauma and/or haemorrhage.

Umbilical Cord Herniation With Small Intestinal Evisceration in Two Thoroughbred Neonates.

This report describes two cases of spontaneous small intestinal evisceration via normally inserted umbilical stumps, without abdominal wall trauma. Both cases occurred immediately following uneventful parturition. The authors believe that these represent cases of umbilical cord herniation. This is a well-recognised condition in humans, but has not been previously described in equines. One foal died before veterinary intervention. The second foal underwent a jejunal resection with end-to-end anastomosis and survived to successfully race. This report describes a previously unrecognised condition and highlights the importance of rapid and appropriate intervention on farm.

Selective terpene based therapeutic deep eutectic systems against colorectal cancer.

Cancer remains a major health problem worldwide, with colorectal cancer (CRC) being the third most incident and the second most lethal. Inflammation, on the other hand, has been highly associated with cancer development and maintenance, therefore, the reduction of the inflammatory microenvironment represents a promising therapeutic strategy. Deep eutectic systems (DES) are based on the combination of different components which together, at a certain molar ratio, present a deep decrease in their melting point compared with the individual compounds. When an active pharmaceutical ingredient is part of a DES it is designated by therapeutic deep eutectic system (THEDES). New THEDES combining terpenes with anticancer properties, such as safranal, menthol and linalool, with nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, ketoprofen and flurbiprofen were produced. To evaluate THEDES anti-CRC therapeutic potential, their physico-chemical properties, bioavailability and bioactivity, were explored. Our results show that safranal:ibuprofen (3:1), safranal:ibuprofen (4:1) and menthol:ibuprofen (3:1) present promising therapeutic activity towards CRC cells due to a selective cytotoxic action towards cancer cells. menthol:ibuprofen (3:1) anti-proliferative action seems to be related with cell membrane disruption, reduction of the inflammation through the reduction of reactive oxygen species (ROS) production, and induction of apoptosis via caspase-3. On the other hand, safranal:ibuprofen (3:1) and safafranal:ibuprofen (4:1) seem to prevent tumour expansion only through the induction of apoptosis via caspase-3. Besides, these systems present an increase in ibuprofen permeability, with menthol:ibuprofen (3:1) increasing also ibuprofen's solubility thus its overall bioavailability. Knowing that cancer is a huge problematic situation that requires alternative therapies with less side effects, improved efficacy, associated with less costs and environmentally friendly, a new opportunity emerges for DES to be part of the pharmaceutical industry.