Editorial for the Special Issue Titled "Design of Polymeric Hydrogels Biomaterials".

Hydrogels have attracted great interest in the biomedical applications field in recent years [...].

Metabolomics perspectives of the ecotoxicological risks of polycyclic aromatic hydrocarbons: A scoping review.

Polycyclic Aromatic Hydrocarbons (PAHs) represent persistent environmental pollutants ubiquitously distributed in the environment. Their presence alongside various other contaminants gives rise to intricate interactions, culminating in profound deleterious consequences. The combination effects of different PAH mixtures on biota remains a relatively unexplored domain. Recent studies have harnessed the exceptional sensitivity of metabolomic techniques to unveil the significant ecotoxicological perils of PAH pollution confronting both human populations and ecosystems. This article furnishes a comprehensive overview of current literature focused on the metabolic repercussions stemming from exposure to complex mixtures of PAHs or PAH-pollution sources using metabolomics approaches. These insights are obtained through a wide range of models, including in vitro assessments, animal studies, investigations on human subjects, botanical specimens, and soil environments. The findings underscore that PAH mixtures induce cellular stress responses and systemic effects, leading to metabolic dysregulations in amino acids, carbohydrates, lipids, and other key metabolites (e.g., organic acids, purines), with specific variations observed based on the organism and PAH compounds involved. Additionally, the ecological consequences of PAH pollutants on plant and soil microbial responses are emphasized, revealing significant changes in stress-related metabolites and nutrient cycling in soil ecosystems. The complex interplay of various PAHs and their metabolic effects on several models, as elucidated through metabolomics, highlight the urgency of further research and the need for comprehensive strategies to mitigate the risks posed by these widespread environmental pollutants.

Pregnancy-Associated Atypical Hemolytic Uremic Syndrome: A Case Report with MCP Gene Mutation and Successful Eculizumab Treatment.

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia and kidney injury from thrombotic microangiopathy. P-aHUS occurs in approximately 1 in 25,000 pregnancies and is strongly related to complement dysregulation and pregnancy-related disorders, such as preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, resulting in adverse perinatal and fetal outcomes. Complement dysregulation in P-aHUS is commonly attributed to genetic mutations or autoantibodies affecting complement factors, including CFH , CFI , and MCP. We present a case of a 25-year-old primigravida who experienced severe preeclampsia and HELLP syndrome followed by the development of complicated P-aHUS during the early postpartum period. The patient exhibited severe clinical manifestations, including hypertensive emergency, central nervous system involvement, renal impairment, and microangiopathic hemolytic anemia. Timely initiation of eculizumab therapy resulted in successful disease remission. Further genetic analysis revealed a likely rare pathogenic MCP gene variant.

Vertebrate damage to Azorean vineyards: the role of the endemic Azores Woodpigeon Columba palumbus azorica.

In the Azores, complaints about grape loss to birds have become recurrent. Although winegrowers frequently blame the endemic Azores Woodpigeon Columba palumbus azorica, data about the magnitude of grape damage and the species responsible for them are lacking. This study provides detailed information about grape damage caused by vertebrates on Pico Island, home to the main wine-growing area of the region. Vineyards were monitored during the ripening period in 2017 and 2018. Damage was assessed by determining the number of plucked, pecked and bitten grapes for a total of 850 bunches. Camera traps were placed in 113 enclosures providing detection and consumption rates of vertebrate species. GLM analysis was performed to test the effect of grape variety, distance to the woods, year and time before harvest on grape damage and consumption events. Damage was estimated at 10.3% (± 0.9) in 2017 and 8.7% (± 0.9) in 2018 and mostly consisted of plucked grapes. Ten vertebrate species were detected consuming grapes. Overall, 524 consumption events were registered. The Madeira lizard Teira dugesii, the Azores Blackbird Turdus merula azorensis and rodents (rats Rattus sp. and the house mouse Mus musculus) were responsible for most of those events. The Azores Woodpigeon accounted for three consumption events. GLM analysis showed that damage was greater in vines adjacent to woods and lower in traditional white varieties. This study constitutes an important baseline for the implementation of efficient measures to mitigate grape predation and sheds light on the minor role of the Azores Woodpigeon in grape damage.

Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

BACKGROUND: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment. RESULTS: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients. CONCLUSIONS: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease.

A new approach for single-haptic retropupillary iris-claw lens subluxation - The "fencing" technique.

INTRODUCTION: Single-haptic iris-claw intraocular lens (IOL) dislocation is not an uncommon complication. A few different surgical techniques are available for its refixation but usually involve a more invasive approach. We aim to demonstrate an original and simple approach for refixation of single haptic retropupillary iris-claw IOL subluxations. METHODS: We present a case of an 80-year-old male with a single haptic retropupillary iris-claw IOL subluxation in a previously vitrectomized eye. We used a new surgical approach to refix this type of subluxation. RESULTS: This new technique uses only two 30-gauge needles (one of them connected to a viscosurgical device) to re-enclavate the subluxated haptic of the retropupillary iris-claw IOL. By minimising surgical manipulation, the patient's postoperative period was uneventful. CONCLUSIONS: We highlight a new, quick, safe, and unusual surgical approach to single-haptic retropupillary iris-claw IOL dislocation in vitrectomized eyes. Because of its characteristics, we named it the "fencing" IOL repositioning technique.

Histological Characteristics of Chronic Allergic Rhinitis Versus Non-allergy: Is There a Difference in the Remodeling?

Demonstrate the histological remodeling changes in the turbinates, identify the frequency of the two forms of rhinitis in the samples studied and determine the remodeling differences found in the two variants. Patients attended an otolaryngology service at the Social Security Hospital of city Sangolqui-Ecuador from February 2016 to June 2017. The allergic variant was determined when eosinophils were found by higher magnification field and non-allergic when they were not found in the submucosal segment. Epithelial, inflammatory, and stromal markers were analyzed. One hundred twenty histopathological samples were analyzed, 75% presented allergic rhinitis, the age averaged 36.2 years. When we compared between the allergic and non-allergic variants: epithelial and stromal markers we had significant differences, as well as between each of its components; except fibrosis. In relation to the inflammatory pattern, there were significant differences between the number of mast cells and stromal markers with eosinophils > 10 by field. The allergic type corresponded to 75% of patients with persistent severe rhinitis who underwent turbinectomy. Regarding remodeling, there was a statistically significant difference in favor of the allergic variant. Eosinophilia greater than 10 was directly related to mastocytosis and subepithelial edema.

Development and validation of predictive equations for spirometry in Portuguese children.

Background: There are no data on lung function reference values for Portuguese children, and the contribution from the Portuguese data set in the Global Lung Function Initiative (GLI) is scant. Objectives: We aimed to estimate new up-to-date reference values for Portuguese children by fitting a multivariable regression model to a general population sample. Further, we intended to assess the external validity of the obtained reference values and to compare them to the GLI reference values. Methods: A random sample of 858 children from 20 primary schools were screened by health questionnaire, physical examination, and spirometry. Spirometric parameters recorded were FVC, FEV1, and FEF25-75. Multiple regression models were used to derive reference equations. Results: Overall, 481 children, aged between 7 and 12 years, 267 boys (55.5%), were included. Boys had higher values for FVC and FEV1 than girls (P < .05). The strongest correlation was found for FVC with height (r = 0.71 for boys and 0.70 for girls), while the lowest correlation was observed in both sexes for FEF25-75 with age (r = 0.23). Height was the most significant predictor of FVC, FEV1, and FEF25-75 in our models. Weight and body mass index were not significant predictors for boys but had a significant effect on girls' equations for all spirometry parameters. Compared to obtained reference equations with GLI, they performed better for FVC in boys, FEV1 in girls, and FEF25-75 in both boys and girls. Conclusion: We offer up-to-date reference values of spirometry for Portuguese children that can be used in clinical practice and research.

Extract2Chip-Bypassing Protein Purification in Drug Discovery Using Surface Plasmon Resonance.

Modern drug discovery relies on combinatorial screening campaigns to find drug molecules targeting specific disease-associated proteins. The success of such campaigns often relies on functional and structural information of the selected therapeutic target, only achievable once its purification is mastered. With the aim of bypassing the protein purification process to gain insights on the druggability, ligand binding, and/or characterization of protein-protein interactions, herein, we describe the Extract2Chip method. This approach builds on the immobilization of site-specific biotinylated proteins of interest, directly from cellular extracts, on avidin-coated sensor chips to allow for the characterization of molecular interactions via surface plasmon resonance (SPR). The developed method was initially validated using Cyclophilin D (CypD) and subsequently applied to other drug discovery projects in which the targets of interest were difficult to express, purify, and crystallize. Extract2Chip was successfully applied to the characterization of Yes-associated protein (YAP): Transcriptional enhancer factor TEF (TEAD1) protein-protein interaction inhibitors, in the validation of a ternary complex assembly composed of Dyskerin pseudouridine synthase 1 (DKC1) and RuvBL1/RuvBL2, and in the establishment of a fast-screening platform to select the most suitable NUAK family SNF1-like kinase 2 (NUAK2) surrogate for binding and structural studies. The described method paves the way for a potential revival of the many drug discovery campaigns that have failed to deliver due to the lack of suitable and sufficient protein supply.

Does the Mediterranean Dietary Pattern Promote Lower Sodium Urinary Excretion in Children?

An adequate sodium intake is related to various health benefits. Parallelly, the Mediterranean diet (MD) is a dietary pattern known for its many positive impacts on health. Nonetheless, the association between adherence to the MD and sodium urinary excretion is scarce, even more in children. This study aimed to assess the association between MD adherence and the excretion of sodium, as a proxy of intake. This cross-sectional analysis comprised 295 children (46.8% females, aged 7-11 years, mean age: 8.53 ± 0.73 years) from 20 schools within Porto, Portugal. MD adherence was evaluated utilizing the alternate Mediterranean score (aMED). Higher scores denote a healthier dietary pattern (0-8). Sodium excretion was estimated by 24-h urine collection. The association between adherence to MD and Na excretion was estimated by logistic regression, adjusting for confounders. Children in the higher sodium excretion group had a higher intake of legumes, a higher body mass index and parents with lower education levels compared to children in the lower sodium excretion group. In logistic regression analysis, sodium urinary excretion was not associated with higher MD adherence, even after adjustment for confounders. High MD adherence could not be associated with lower sodium excretion in children.

Effect of varying functional monomers in experimental self-adhesive composites: polymerization kinetics, cell metabolism influence and sealing ability.

The aim was to evaluate the effects of adding different functional monomers to experimental self-adhesive composites (SACs) on polymerization kinetics, cell metabolic activity, and sealing ability. SACs were formulated using urethane dimethacrylate as the base monomer and triethylene glycol dimethacrylate. Additionally, 10 wt.% of distinct functional monomers were added - 10-methacryloyloxydecyl dihydrogen phosphate, glycerol phosphate dimethacrylate (GPDM), 2-hydroxyethyl methacrylate (HEMA) or hydroxyethyl acrylamide (HEAA). ATR-FTIR was used to determine real-time polymerization kinetics (20 min,n= 3). The final extrapolated conversion and polymerization rates were determined (DC,max;Rp,max). TheDC,maxvalues were employed to calculate volumetric shrinkage. The MTT assay was performed on MDPC-23 cells using disc extracts at different concentrations (n= 8). Class V cavities were prepared in 60 sound human molars, assigned to six groups (n= 10), depending on the composite used and aging type (T0 or TC, if thermocycled for 10 000 cycles). One-way ANOVA, two-way, andKruskal-Wallistests were employed to treat the data (ɑ= 0.05). Varying the functional monomers had a large impact on DC,max, as confirmed by one-way ANOVA (p<0.001). The highest was obtained for HEMA (64 ± 3%). The HEMA and HEAA formulations were found to be significantly more toxic at concentrations below 100%. For microleakage, having a functional monomer or not did not show any improvement, irrespective of margin or aging period (Mann-Whitney U,p> 0.05). Larger functional monomers MDP and GPDM affected polymerization properties. Conversely, their acidity did not seem to be detrimental to cell metabolic activity. Regarding sealing ability, it seems that the functional monomers did not bring an advantage to the composites. Varying the functional monomer in SACs had a clear impact on the polymerization kinetics as well as on their cytotoxic potential. However, it did not confer better microleakage and sealing. Claiming self-adhesiveness based only on functional monomers seems dubious.

Mediterranean Diet and Airway Inflammation in School-Aged Children.

There seems to exist an intricate relationship between airway inflammation, body mass index (BMI), and diet. The intake of specific foods or food groups has been suggested to suppress the oxidative stress and inflammatory processes that characterize airway inflammation, but little is known about dietary patterns and their complex interplay with BMI and airway inflammation. Therefore, this cross-sectional study aimed to explore the association between adherence to the Mediterranean diet (MD), a characteristic European diet, and levels of airway inflammation in school-aged children, taking into account their BMI. This cross-sectional analysis comprised 660 children: 49.1% females, 7-12 years old. Adherence to the MD was assessed through the alternate Mediterranean score (aMED). Higher scores represent a healthier diet (0-8). Airway inflammation was assessed measuring exhaled fractional nitric oxide (eNO). Two categories of BMI were considered: non-overweight/non-obese (p < 85th) and overweight/obese (p ≥ 85th). The associations between diet and airway inflammation were estimated using logistic regression models. Higher scores of the aMED were associated with decreased odds of having eNO ≥ 35 ppb, but only in non-overweight/non-obese children (OR = 0.77; 95% CI, 0.61-0.97). For overweight/obese children, the previous association was not significant (OR = 1.57, 95% CI, 0.88-2.79). Our findings suggest that adherence to the MD is associated with lower levels of airway inflammation among non-overweight/non-obese children.

Real-time assessment of H. pylori during the endoscopic assessment of individuals with gastric intestinal metaplasia: a possible way to reduce the burden of care.

OBJECTIVES: The management of individuals with gastric intestinal metaplasia (GIM) includes biopsies for its staging and to diagnose Helicobacter pylori (Hp ). Advanced-stage GIM can be estimated by endoscopy through EGGIM, and a new device permits the real-time assessment of ammonia for the identification of Hp infection. The aim of this study was to assess the simultaneous use of EGGIM and real-time assessment of ammonia to avoid biopsies and reduce the burden of care in clinical practice. METHODS: A multicentre study involving 101 consecutively enrolled patients [52% male; 65(18-85) years]. During endoscopy, gastric juice was aspirated and analysed; EGGIM was determined in real-time. Targeted biopsies were performed and histopathological assessment was used as gold standard. RESULTS: Advanced-stage GIM were detected in 14.9% of patients and Hp infection in 18.8%. EGGIM showed for advanced-stage GIM a sensitivity, specificity and NPV of 86.7%, 84.9% and 97.3%, whilst real-time assessment of ammonia, 83.3%, 78.2% and 95.4%, respectively. Gastric juice was insufficient in 5 (5.0%). Overall, 64 (67%) patients were correctly diagnosed by EGGIM and real-time assessment of ammonia. If the 47 (49%) patients negative to both assessments would have avoided biopsies, only 4 (4.2%) would have been missed: two with advanced-stage GIM and two with Hp infection. CONCLUSION: The combination of endoscopic assessment and real-time analysis of Hp allows the exclusion of advanced-stage GIM or Hp infection without the need of biopsies in a significant proportion of individuals. This may allow in specific situations to abstain from biopsies reducing the burden of care.

The difficulties in emotion regulation scale: Dimensionality, measurement invariance, and physiological correlates in community adolescents.

OBJECTIVE: Emotion regulation is a central construct for the study of mental health in adolescence. Although the Difficulties in Emotion Regulation Scale (DERS) has been vastly used, several issues remain unanswered (e.g., factor structure/dimensionality). This study aimed to validate the 36-items DERS in a sample of 989 Portuguese community adolescent (460 boys; 529 girls; age ranged from 14 to 18). METHOD: A bifactor-ESEM model, comprising a general and six specific factors (nonacceptance; goals; impulses; strategies; clarity; awareness) was explored and considered the best fitting model. RESULTS: Gender measurement invariance was established. When compared with boys, although differences were small in magnitude, girls presented higher emotion regulation difficulties. Evidence for reliability and construct/temporal validity were found, and significant associations between the DERS and physiological measures of emotion regulation (i.e., Heart Rate and Heart Rate Variability) were established. CONCLUSION: Findings support the use of the DERS in adolescent samples.

Temperature effect in the inhibition of PLA2 activity of Bothrops brazili venom by Rosmarinic and Chlorogenic acids, experimental and computational approaches.

Myotoxicity caused by snakebite envenoming emerges as one of the main problems of ophidic accidents as it is not well neutralized by the current serum therapy. A promising alternative is to search for efficient small molecule inhibitors that can act against multiple venom components. Phospholipase A2 (PLA2) is frequently found in snake venom and is usually associated with myotoxicity. Thus it represents an excellent target for the search of new treatments. This work reports the effect of temperature in the inhibition of catalytic properties of PLA2 from Bothrops brazili venom by Rosmarinic (RSM) and Chlorogenic (CHL) acids through experimental and computational approaches. Three temperatures were evaluated (25, 37 and 50 °C). In the experimental section, enzymatic assays showed that RSM is a better inhibitor in all three temperatures. At 50 °C, the inhibition efficiency decayed significantly for both acids. Docking studies revealed that both ligands bind to the hydrophobic channel of the protein dimer where the phospholipid binds in the catalytic process, interacting with several functional residues. In this context, RSM presents better interaction energies due to stronger interactions with chain B of the dimer. Molecular dynamics simulations showed that RSM can establish selective interactions with ARG112B of PLA2, which is located next to residues of the putative Membrane Disruption Site in PLA2-like structures. The affinity of RSM and CHL acids towards PLA2 is mainly driven by electrostatic interactions, especially salt bridge interactions established with residues ARG33B (for CHL) and ARG112B (RSM) and hydrogen bonds with residue ASP89A. The inability of CHL to establish a stable interaction with ARG112B was identified as the reason for its lower inhibition efficiency compared to RSM at the three temperatures. Furthermore, extensive structural analysis was performed to explain the lower inhibition efficiency at 50 °C for both ligands. The analysis performed in this work provides important information for the future design of new inhibitors.Communicated by Ramaswamy H. Sarma.

Intestinal infection triggers mitochondria-mediated α-synuclein pathology: relevance to Parkinson's disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative disease characterized by the loss of dopaminergic neurons in the midbrain. In the prodromal phase several autonomic symptoms including orthostatic hypotension and constipation are correlated with increased α-synuclein pathology in peripheral tissues. It is currently accepted that some idiopathic PD cases may start in the gut (body-first PD) with accumulation of pathological α-synuclein in enteric neurons that may subsequently propagate caudo-rostrally to the central nervous system. In addition to the already-established regulation of synaptic vesicle trafficking, α-synuclein also seems to play a role in neuronal innate immunity after infection. Our goal was to understand if seeding the gut with the foodborne pathogen Listeria monocytogenes by oral gavage would impact gut immunity and eventually the central nervous system. Our results demonstrate that L. monocytogenes infection induced oligomerization of α-synuclein in the ileum, along with a pronounced pro-inflammatory local and systemic response that ultimately culminated in neuronal mitochondria dysfunction. We propose that, having evolved from ancestral endosymbiotic bacteria, mitochondria may be directly targeted by virulence factors of intracellular pathogens, and that mitochondrial dysfunction and fragmentation resulting also from the activation of the innate immune system at the gut level, trigger innate immune responses in midbrain neurons, which include α-synuclein oligomerization and neuroinflammation, all of which hallmarks of PD.

Primary cilia shape hallmarks of health and aging.

Primary cilia are specialized organelles that sense changes in extracellular milieu, and their malfunction is responsible for several disorders (ciliopathies). Increasing evidence shows that primary cilia regulate tissue and cellular aging related features, which led us to review the evidence on their role in potentiating and/or accelerating the aging process. Primary cilia malfunction is associated with some age-related disorders, from cancer to neurodegenerative and metabolic disorders. However, there is limited understanding of molecular pathways underlying primary cilia dysfunction, resulting in scarce ciliary-targeted therapies available. Here, we discuss the findings on primary cilia dysfunction as modulators of the health and aging hallmarks, and the pertinence of ciliary pharmacological targeting to promote healthy aging or treat age-related diseases.