In vivo biocompatibility testing of nanoparticle-functionalized alginate-chitosan scaffolds for tissue engineering applications.

Background: There is a strong interest in designing new scaffolds for their potential application in tissue engineering and regenerative medicine. The incorporation of functionalization molecules can lead to the enhancement of scaffold properties, resulting in variations in scaffold compatibility. Therefore, the efficacy of the therapy could be compromised by the foreign body reaction triggered after implantation. Methods: In this study, the biocompatibilities of three scaffolds made from an alginate-chitosan combination and functionalized with gold nanoparticles (AuNp) and alginate-coated gold nanoparticles (AuNp + Alg) were evaluated in a subcutaneous implantation model in Wistar rats. Scaffolds and surrounding tissue were collected at 4-, 7- and 25-day postimplantation and processed for histological analysis and quantification of the expression of genes involved in angiogenesis, macrophage profile, and proinflammatory (IL-1ß and TNFα) and anti-inflammatory (IL-4 and IL-10) cytokines. Results: Histological analysis showed a characteristic foreign body response that resolved 25 days postimplantation. The intensity of the reaction assessed through capsule thickness was similar among groups. Functionalizing the device with AuNp and AuNp + Alg decreased the expression of markers associated with cell death by apoptosis and polymorphonuclear leukocyte recruitment, suggesting increased compatibility with the host tissue. Similarly, the formation of many foreign body giant cells was prevented. Finally, an increased detection of alpha smooth muscle actin was observed, showing the angiogenic properties of the elaborated scaffolds. Conclusion: Our results show that the proposed scaffolds have improved biocompatibility and exhibit promising potential as biomaterials for elaborating tissue engineering constructs.

Effects of polymethylmethacrylate nanoplastics on the polychaete Hediste diversicolor: Behavioural, regenerative, and biochemical responses.

Plastics, particularly microplastics (MPs) and nanoplastics (NPs), have been regarded as pollutants of emerging concern due to their effects on organisms and ecosystems, especially considering marine environments. However, in terms of NPs, there is still a knowledge gap regarding the effects of size and polymer on marine invertebrates, such as benthic organisms. Therefore, this study aimed to understand, regarding behavioural, physiological, and biochemical endpoints (neurotransmission, energy metabolism, antioxidant status, and oxidative damage), the effects of 50 nm waterborne polymethylmethacrylate (PMMA) NPs (0.5 to 500 µg/L) on the marine benthic polychaete Hediste diversicolor, a key species in estuarine and coastal ecosystems. Results demonstrated that worms exposed to PMMA NPs had a shorter burrowing time than control organisms. Nevertheless, worms exposed to PMMA NPs (0.5 and 500 µg/L) decreased cholinesterase activity. Energy metabolism was decreased at 50 and 500 µg/L, and glycogen content decreased at all concentrations of PMMA NPs. Enzymes related to the antioxidant defence system (superoxide dismutase and glutathione peroxidase) displayed increased activities in H. diversicolor specimens exposed to concentrations between 0.5 and 500 µg/L, which led to no damage at the cell membrane and protein levels. In this study, polychaetes also displayed a lower regenerative capacity when exposed to PMMA NPs. Overall, the data obtained in this study emphasize the potential consequences of PMMA NPs to benthic worms, particularly between 0.5 and 50 µg/L, with polychaetes exposed to 50 µg/L being the most impacted by the analysed NPs. However, since sediments are considered to be sinks and sources of plastics, further studies are needed to better understand the impacts of different sizes and polymers on marine organisms, particularly benthic species.

The impact of chemical pollution on the European eel (Anguilla anguilla) from a Mediterranean hypersaline coastal lagoon.

The European eel (Anguilla anguilla) is a critically endangered species. The impact of environmental contamination on this species has been highlighted as contributing to the decline in recruitment. The Mar Menor hypersaline coastal lagoon (SE Spain) is one of the most productive fisheries of European eel in Europe, making it a critical habitat for species conservation. The present study aimed to provide an initial overview of the impact of organic chemical contaminants on the European eel and the potential sublethal effects of chemical pollution on pre-migrating eels in this hypersaline habitat. We investigated muscle bioaccumulation of main persistent and hazardous organic contaminants (including some current-use pesticides) and genotoxicity, neurotoxicity, and xenobiotic detoxification system responses. The findings show that lagoon eels were exposed to high levels of legacy organochlorine contaminants, recently banned pesticides (chlorpyrifos), and some emerging chemicals. Some individuals surpassed the maximum levels of CBs authorized by the European Commission for human consumption. In this species, residuals of chlorpyrifos, pendimethalin, and chlorthal dimethyl have been reported for the first time. This field study provides relevant data to stock management and human health consumption and provides the first biomarker responses in European eel under permanent hypersaline conditions. Furthermore, the high frequency of micronuclei in peripheral erythrocytes of lagoon eels indicates sublethal genotoxic effects on the organism. Overall, the European eels growing and maturing in the Mar Menor lagoon are exposed to toxic and carcinogenic chemicals. The lack of seafood safety regulations for human consumption for some legacy chemicals that were measured in high concentrations in our study requires special action. Further biomonitoring and research are recommended to protect the animal, public, and environmental health.

Embryonic Hyperglycemia Disrupts Myocardial Growth, Morphological Development, and Cellular Organization: An In Vivo Experimental Study.

Hyperglycemia during gestation can disrupt fetal heart development and increase postnatal cardiovascular disease risk. It is therefore imperative to identify early biomarkers of hyperglycemia during gestation-induced fetal heart damage and elucidate the underlying molecular pathomechanisms. Clinical investigations of diabetic adults with heart dysfunction and transgenic mouse studies have revealed that overexpression or increased expression of TNNI3K, a heart-specific kinase that binds troponin cardiac I, may contribute to abnormal cardiac remodeling, ventricular hypertrophy, and heart failure. Optimal heart function also depends on the precise organization of contractile and excitable tissues conferred by intercellular occlusive, adherent, and communicating junctions. The current study evaluated changes in embryonic heart development and the expression levels of sarcomeric proteins (troponin I, desmin, and TNNI3K), junctional proteins, glucose transporter-1, and Ki-67 under fetal hyperglycemia. Stage 22HH Gallus domesticus embryos were randomly divided into two groups: a hyperglycemia (HG) group, in which individual embryos were injected with 30 mmol/L glucose solution every 24 h for 10 days, and a no-treatment (NT) control group, in which individual embryos were injected with physiological saline every 24 h for 10 days (stage 36HH). Embryonic blood glucose, height, and weight, as well as heart size, were measured periodically during treatment, followed by histopathological analysis and estimation of sarcomeric and junctional protein expression by western blotting and immunostaining. Hyperglycemic embryos demonstrated delayed heart maturation, with histopathological analysis revealing reduced left and right ventricular wall thickness (-39% and -35% vs. NT). Immunoexpression levels of TNNI3K and troponin 1 increased (by 37% and 39%, respectively), and desmin immunofluorescence reduced (by 23%). Embryo-fetal hyperglycemia may trigger an increase in the expression levels of TNNI3K and troponin I, as well as dysfunction of occlusive and adherent junctions, ultimately inducing abnormal cardiac remodeling.

Human Heart Morphogenesis: A New Vision Based on In Vivo Labeling and Cell Tracking.

Despite the extensive information available on the different genetic, epigenetic, and molecular features of cardiogenesis, the origin of congenital heart defects remains unknown. Most genetic and molecular studies have been conducted outside the context of the progressive anatomical and histological changes in the embryonic heart, which is one of the reasons for the limited knowledge of the origins of congenital heart diseases. We integrated the findings of descriptive studies on human embryos and experimental studies on chick, rat, and mouse embryos. This research is based on the new dynamic concept of heart development and the existence of two heart fields. The first field corresponds to the straight heart tube, into which splanchnic mesodermal cells from the second heart field are gradually recruited. The overall aim was to create a new vision for the analysis, diagnosis, and regionalized classification of congenital defects of the heart and great arteries. In addition to highlighting the importance of genetic factors in the development of congenital heart disease, this study provides new insights into the composition of the straight heart tube, the processes of twisting and folding, and the fate of the conus in the development of the right ventricle and its outflow tract. The new vision, based on in vivo labeling and cell tracking and enhanced by models such as gastruloids and organoids, has contributed to a better understanding of important errors in cardiac morphogenesis, which may lead to several congenital heart diseases.

Pediatric cutaneous mucormicosis.

A 9-year-old boy diagnosed with acute myeloblastic leukemia and undergoing chemotherapy, was admitted with febrile neutropenia. During his admission, several violaceous plaques appeared on the upper extremities and anterior left hemithorax, which worsened and acquired a necrotic center. We performed a biopsy and histology showed a cutaneous infarction at the dermoepidermal and subcutaneous level. We observed abundant wide hyphae with right-angled branching and a culture isolated Rhizopus oryzae. A plastic surgery consultant performed a surgical debridement of the lesions and treatment was started with intravenous amphotericin B. The patient did well on treatment and after almost a month of hospitalization, he was discharged with oral posaconazole. Mucormycosis is an opportunistic fungal infection associated with immunosuppression, particularly involving prematurity and hematological diseases in the pediatric age group. Multiple lesions, as in our case, are infrequent. The clinical presentation is variable. Direct smear or histological observation is the quickest diagnostic technique whereas culture is the most definitive. The combination of surgical debridement and amphotericin B is the treatment with the highest survival rates.

Sodium Alginate/Chitosan Scaffolds for Cardiac Tissue Engineering: The Influence of Its Three-Dimensional Material Preparation and the Use of Gold Nanoparticles.

Natural biopolymer scaffolds and conductive nanomaterials have been widely used in cardiac tissue engineering; however, there are still challenges in the scaffold fabrication, which include enhancing nutrient delivery, biocompatibility and properties that favor the growth, maturation and functionality of the generated tissue for therapeutic application. In the present work, different scaffolds prepared with sodium alginate and chitosan (alginate/chitosan) were fabricated with and without the addition of metal nanoparticles and how their fabrication affects cardiomyocyte growth was evaluated. The scaffolds (hydrogels) were dried by freeze drying using calcium gluconate as a crosslinking agent, and two types of metal nanoparticles were incorporated, gold (AuNp) and gold plus sodium alginate (AuNp+Alg). A physicochemical characterization of the scaffolds was carried out by swelling, degradation, permeability and infrared spectroscopy studies. The results show that the scaffolds obtained were highly porous (>90%) and hydrophilic, with swelling percentages of around 3000% and permeability of the order of 1 × 10−8 m2. In addition, the scaffolds proposed favored adhesion and spheroid formation, with cardiac markers expression such as tropomyosin, troponin I and cardiac myosin. The incorporation of AuNp+Alg increased cardiac protein expression and cell proliferation, thus demonstrating their potential use in cardiac tissue engineering.

Both Zn biofortification and nutrient distribution pattern in cherry tomato plants are influenced by the application of ZnO nanofertilizer.

A pot experiment was conducted to determine the influence of commercial nanoparticles (ZnO-NPs) at different doses for use as nanofertilizer on nutrient uptake and its distribution in cherry tomato (Solanum lycopersicum L var. cerasiforme) plants in an acidic (soil pH 5.5) and calcareous soil (soil pH 8.5) from the Mediterranean area. We determined crop yield; macro- (N, P, K, Mg, S and Ca) and micro-nutrient (B, Cu, Fe, Mn, Na and Zn) concentrations in the different parts of the crop (root, stem, leaves and tomato fruits) and the extent of nutrient translocation to the aerial part of the plant. The concentrations of macronutrients N, P, K and Mg in tomato fruits grown in both soils can be considered adequate in terms of nutritional requirements. However, the Ca concentration in tomato fruits grown in the calcareous soil did not reach the required concentration to be considered sufficient. This effect was related to the characteristics of this calcareous soil. Although different concentrations of ZnO-NPs did not affect Fe and Na concentrations in tomato fruit, B concentration in tomato fruits increased with the application of ZnO-NPs. In addition, Cu concentration decreased with the application of ZnO-NPs compared to treatments without any Zn application (Nil-ZnO NP) in the calcareous soil. Manganese concentrations decreased with ZnO-NPs application in both soils. The effect of the application of ZnO-NPs depends on soil characteristics. Zinc applied as a nanofertilizer in the form of ZnO-NPs can be used to increase the crop yield and to obtain an adequate Zn biofortification in cherry tomato crop. The Zn concentrations in tomato fruits reached ranges of 4.5-4.8 mg Zn kg-1 in the acidic soil and 2.5-3,5 mg Zn kg-1 in the calcareous soil. Nutrient concentrations in these fruits following biofortification are adequate for human consumption.

Does parental exposure to nanoplastics modulate the response of Hediste diversicolor to other contaminants: A case study with arsenic.

Plastic pollution is a serious problem in aquatic systems throughout the world. Despite the increasing number of studies addressing the impact of macro- and microplastics on biota, there is still a significant knowledge gap regarding the effects of nanoplastics alone and in combination with other contaminants. Among the aquatic contaminants that may interact with nanoplastics is arsenic (As), a metalloid found in estuarine and coastal ecosystems, pernicious to benthic organisms. This study aimed to understand how a parental pre-exposure to 100 nm polystyrene nanoplastics (PS NPs) would influence the response of Hediste diversicolor to exposure to arsenic in terms of behaviour, neurotransmission, antioxidant defences and oxidative damage, and energy metabolism. The obtained data revealed an increase in burrowing time and a significant inhibition in cholinesterase activity in all polychaetes exposed to As, regardless of the pre-exposure to PS NPs. Oxidative status was altered particularly in parentally exposed organisms, with damage detected in terms of lipid peroxidation at 50 µg/L and protein carbonylation at 50 and 250 µg As/L exposed organisms when compared to control. Overall, data shows that parental pre-exposure to plastics influences the response of aquatic organisms, increasing their susceptibility to other contaminants. Thus, more studies should be performed with other environmental contaminants, to better understand the potential increased risk associated with the presence of nanoplastics to aquatic ecosystems.

Adherence to endoscopic surveillance for advanced lesions and colorectal cancer in inflammatory bowel disease: an AEG and GETECCU collaborative cohort study.

BACKGROUND AND AIMS: Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non-adherence. METHODS: A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1 year). Cox-proportional regression analyses were used to compare the risk of lesions. p-values below 0.05 were considered significant. RESULTS: A total of 1031 patients (732 ulcerative colitis, 259 Crohn's disease and 40 indeterminate colitis; mean age of 36 ± 15 years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI = 24-29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR = 3.59; 95% CI = 1.3-10.1; p = 0.016). Risk of delay or non-performance of endoscopic follow-up was higher as risk groups increased (OR = 3.524; 95% CI = 2.462-5.044; p < 0.001 and OR = 4.291; 95%CI = 2.409-7.644; p < 0.001 for intermediate- and high- vs low-risk groups). CONCLUSIONS: Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence.

Empleo de la vía subcutánea en un hospital de segundo nivel. Revisión del uso actual y nuevas propuestas / Use of the subcutaneous route in a second level hospital. A review of current use and new proposals

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Sources, Characteristics, and Therapeutic Applications of Mesenchymal Cells in Tissue Engineering.

Tissue engineering (TE) is a therapeutic option within regenerative medicine that allows to mimic the original cell environment and functional organization of the cell types necessary for the recovery or regeneration of damaged tissue using cell sources, scaffolds, and bioreactors. Among the cell sources, the utilization of mesenchymal cells (MSCs) has gained great interest because these multipotent cells are capable of differentiating into diverse tissues, in addition to their self-renewal capacity to maintain their cell population, thus representing a therapeutic alternative for those diseases that can only be controlled with palliative treatments. This review aimed to summarize the state of the art of the main sources of MSCs as well as particular characteristics of each subtype and applications of MSCs in TE in seven different areas (neural, osseous, epithelial, cartilage, osteochondral, muscle, and cardiac) with a systemic revision of advances made in the last 10 years. It was observed that bone marrow-derived MSCs are the principal type of MSCs used in TE, and the most commonly employed techniques for MSCs characterization are immunodetection techniques. Moreover, the utilization of natural biomaterials is higher (41.96%) than that of synthetic biomaterials (18.75%) for the construction of the scaffolds in which cells are seeded. Further, this review shows alternatives of MSCs derived from other tissues and diverse strategies that can improve this area of regenerative medicine.

The role of procalcitonin as a prognostic factor for acute cholangitis and infections in acute pancreatitis: a prospective cohort study from a European single center.

BACKGROUND: Infection in acute pancreatitis will worsen the disease prognosis. The aim of our study was to analyze the role of procalcitonin as a prognostic biomarker for infections and clinical severity. METHOD: A prospective single-cohort observational study of patients diagnosed of acute pancreatitis (n = 152) was designed. PCT determination was tested on admission (first 72 h). Infections (biliary, extrapancreatic and infected pancreatic necrosis), need for antibiotics, urgent ERCP and severity scores for acute pancreatitis was assessed. ROC curves were designed and the area under the curve was calculated. Logistic regression for multivariate analysis was performed to evaluate the association between procalcitonin optimal cut-off level and major complications. RESULTS: PCT >0.68 mg/dL had higher incidence of global infection, acute cholangitis, bacteraemia, infected pancreatic necrosis, use of antibiotics in general, and need for urgent ERCP. In the multivariate regressions analysis, PCT >0.68 mg/dL at admission demonstrated to be a strong risk factor for complications in acute pancreatitis. DISCUSSION: PCT levels can be used as a reliable laboratory test to predict infections and the clinical severity of acute pancreatitis. High levels of PCT predict antibiotics prescription as well as the need for urgent ERCP in patients with concomitant clinically severe cholangitis.

The influence of natural vs anthropogenic factors on trace metal(loid) levels in the Mussel Watch programme: Two decades of monitoring in the Spanish Mediterranean sea.

The spatial distribution and temporal trends of trace metals (i.e. Cd, Cu, Hg, Pb and Zn) and a metalloid (i.e. As) along the Spanish Mediterranean coast from 1993 to 2013 are presented with a new estimation of their background levels monitored using wild mussels. Over a 20 years period, yearly mussel monitoring was undertaken with a rigorous field sampling protocol using 3 pooled samples strategy (3 x n = 80, with 8 mussels in the 3.0 to 3.9 size categories at each site), obtained in the pre-spawning period (May-June) to minimize biological factors and seasonal variability, which is a fundamental element of the international programme. Spatial distribution was characterized every 5 years and temporal trends were determined in 11 locations. The main aims of the present long term study are to evaluate the environmental status of different coastal locations regarding trace metal levels and follow the evolution of these levels over time after the implementation of regulatory measures. Regarding spatial distribution, the highest values for Cd, Cu, Hg and Pb were found close to known highly anthopogenic cities or shipyard areas. However, As and Zn did not strictly follow this pattern, showing natural increased concentrations in the Levantine Balearic and Strait of Gibraltar-Alboran Sea demarcations respectively. These distributions are associated with the conjunction of two geological formation inputs (Massif Central in France and Iberian Pyritic Belt in Spain) and the oceanographic conditions in the adjacent coastal area. In the case of temporal trends, metal concentrations decreased significantly over time in most stations, confirming the effectiveness of the regulatory measures and prohibitions established under European legislation. Concentrations of Pb were above the established thresholds for human consumption in only 12-14% of the sampling areas. With the information obtained for this study, we estimate background concentrations and propose new Background Assesment Criteria (BAC) for the Spanish Mediterranean coast as a threshold criterion: 1.62 mg/kg d.w. for Cd, 8.75 mg/kg d.w. for Cu, 0.202 mg/kg d.w. for Hg and 2.83 mg/kg d.w. for Pb. Exceptions should exist for As and Zn, for which there should be different levels in each demarcation, due to the geological, hydrological and oceanographic peculiarities of the Spanish coast. For the Levantine-Balearic demarcation, the proposed background concentrations are 117 mg/kg d.w. for As and 200 mg/kg d.w. for Zn., whereas in the Strait of Gibraltar-Alboran Sea demarcation, they are 27.5 mg/kg d.w. for As, and 471 mg/kg d.w. for Zn. This work demonstrates the vital importance of defining the background levels of metal(loid)s at a regional or subregional level because, for areas not affected by anthropogenic causes which have high values as the result of natural processes, this would avoid the risk of constantly surpassing the levels proposed in directives.

Serum cholesterol predicts transplant-free survival in cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND: Malnutrition is frequent in patients with cirrhosis and has been associated with poor prognosis. The Model for End-stage Liver Disease (MELD) score was created to predict survival after Transjugular Intrahepatic Porto-systemic Shunt (TIPS) but lacks a nutritional parameter. AIMS: To evaluate the prognostic value of serum cholesterol in patients with cirrhosis undergoing TIPS and to develop a prognostic score to predict survival. METHODS: An explorative cross-sectional study was conducted of cirrhotic patients undergoing TIPS from 2008 until 2019. Exclusion criteria were liver transplantation or hepatocellular carcinoma before TIPS. Risk analysis was used to compare survival according to clinical and analytical data. The diagnostic performance of serum cholesterol added to MELD was evaluated and confirmed in an external validation cohort. RESULTS: The final cohort of 100 patients had a mean MELD score of 14±5 and cholesterol of 122±51 mg/dL. MELD (p < 0,05) and both cholesterol (p < 0,05) and low-density lipoprotein levels (LDL-C) (p < 0,05) were independent predictors of post-TIPS transplant-free survival with an optimal cut-off of 106 mg/dL for serum cholesterol. The combined MELD-cholesterol risk score improved diagnostic accuracy of each parameter separately, and this was confirmed in the external cohort. CONCLUSION: Serum cholesterol and LDL-C are independent predictors of transplant-free survival in cirrhotic patients undergoing TIPS. The MELD-cholesterol score slightly improved prognostic accuracy. LAY SUMMARY: As an objective and easily measured indicator of both nutritional status and hepatic function, serum cholesterol could be useful to predict transplant-free survival in patients with cirrhosis undergoing TIPS. It can enable health care providers to identify high-risk patients and to optimize nutritional status before TIPS.