Cyclic fatigue resistance of two pediatric rotary files manufactured with different heat treatments: an in-vitro study.

Nickel-titanium (NiTi) instruments offer many advantages during endodontic instrumentation; however, the fracture risk within the canal remains a concern. Manufacturers continuously develop and introduce instruments to the market with supposedly enhanced cyclic fatigue resistance and increased flexibility, achieved through different proprietary manufacturing processes, the details of which have not been made public. In recent years, two rotary systems specially designed for deciduous teeth have been commercially available, but information about their performance is lacking. This investigation aimed to identify which manufacturing process provides better cyclic fatigue resistance: the AF-H Wire technology used in the AF baby rotary files (AF-f) or the CM-Wire technology used in the i3 Gold deciduous teeth rotary files (i3G-f). Forty rotary International Organization for Standardization (ISO) 25/04 files were tested in artificial canals with a standard geometry of 60° angle and 2.5 mm radius until fracture. The number of cycles to fracture was calculated, and the length of the fragments was measured. A scanning electron microscope (SEM) was used to examine the fracture surfaces and fragments. Energy dispersive spectroscopy (EDS) was used to determine the percentage weight of NiTi in each file. The statistical analysis (Mann-Whitney test) showed that the cyclic fatigue resistance of the AF-f was significantly higher (p < 0.0001) than that of the i3G-f. Additionally, there was a significant difference (p = 0.0419) in the length of the fractured fragments. All instruments showed one or more types of manufacturing defects and presented similar NiTi percentages by weight. The manufacturing process is critical to cyclic fatigue resistance, and there seems to be responsible for the difference in cyclic fatigue resistance between these similar instruments.

Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington disease models.

Huntington disease (HD) is a fatal neurodegenerative disease caused by a trinucleotide repeat expansion in exon 1 of the huntingtin gene (HTT) resulting in toxic gain-of-function and cell death. Despite its monogenic cause, the pathogenesis of HD is highly complex and increasing evidence indicates that, in addition to the full-length (FL) mutant HTT protein, the expanded exon 1 HTT (HTTexon1) protein that is translated from the HTT1a transcript generated by aberrant splicing is prone to aggregate and may contribute to HD pathology. This finding suggests that reducing the expression of HTT1a may achieve a greater therapeutic benefit than targeting only FL mutant HTT. Conversely, strategies that exclusively target FL HTT may not fully prevent the pathogenesis of HD. We have developed an engineered microRNA targeting the HTT exon 1 sequence (miHTT), delivered via adeno-associated virus serotype 5 (AAV5). The target sequence of miHTT is present in both FL HTT and HTT1a transcripts. Preclinical studies with AAV5-miHTT have demonstrated efficacy in several rodent and large animal models by reducing FL HTT mRNA and protein and rescuing HD-like phenotypes, and have been the rationale for phase I/II clinical studies now ongoing in the US and Europe. In the present study, we evaluated the ability of AAV5-miHTT to reduce the levels of aberrantly spliced HTT1a mRNA and the HTTexon1 protein in the brain of two mouse models of HD (heterozygous zQ175 knock-in mice and humanized Hu128/21 mice). Polyadenylated HTT1a mRNA and HTTexon1 protein were detected in the striatum and cortex of heterozygous zQ175 knock-in mice, but not in wild-type, littermate control mice. Intrastriatal administration of AAV5-miHTT resulted in dose-dependent expression of mature miHTT microRNA in cortical brain regions, accompanied by significant lowering of both FL HTT and HTT1a mRNA expression at two months post-injection. Mutant HTT and HTTexon1 protein levels were also significantly reduced in the striatum and cortex of heterozygous zQ175 knock-in at 2 months after AAV5-miHTT treatment and in humanized Hu128/21 mice 7 months post-treatment. The effects were confirmed in primary Hu128/21 neuronal cultures. These results demonstrate that AAV5-miHTT gene therapy is an effective approach to lower both FL HTT and the pathogenic HTTexon1 levels, which could potentially have an additive therapeutic benefit compared to other HTT-targeting modalities.

Prospective Study: Utility of Anterior Segment Optical Coherence Tomography to Identify Predictive Factors of Recurrence in Pterygium Surgery.

Background/Objectives: The main purpose of this study is to determine, by anterior segment optical coherence tomography (AS-OCT), the anatomical characteristics, both preoperatively and postoperatively, that correlate with a higher rate of pterygium recurrence after surgery with exeresis and conjunctival autograft with biological glue. Methods: A total of 50 eyes which were listed for primary pterygium surgery at an ophthalmology tertiary centre were treated with standard pterygium excision and a conjunctival autograft with tissue glue. Ten variables were measured with AS-OCT (Casia 2; Tomey Corp., Nagoya, Japan) during six control visits with all patients. Finally, statistical analysis was performed using SPSS (SPSS stadistics®, IBM®, version 21.0.0.0) for descriptive variables and R-project (The R foundation©, version 3.0.2) for the rest of the analyses, including a descriptive analysis and an inferential analysis studying prognostic factors of recurrence and their predictive capacity. Results: Among the 50 patients who underwent surgery, recurrence was detected in 8 cases (rate 16%; 95% CI: 5.8-26.2%). Most cases (n = 6) were detected 3 months after surgery. The pattern of recurrences was atrophic in two thirds of the cases; none required reintervention. Preoperative total conjunctival thickness at 3 mm was significantly increased in patients who developed recurrence. One week after surgery, epithelial and stromal thickness at 1 mm and total thickness at 3 mm proved to be useful for predicting recurrence. Both models have significant discriminant capacity. Conclusions: By imaging the graft with AS-OCT preoperatively and 7 days after surgery, the risk of future recurrence can be predicted.

Systematic Review and Metanalysis of the Expression of Blood-Based and Cerebrospinal Fluid-Based Biomarkers Related to Inflammatory Mediators in Neuropathic Pain.

BACKGROUND: The understanding of neuropathic pain remains incomplete, highlighting the need for research on biomarkers for improved diagnosis and treatment. This review focuses on identifying potential biomarkers in blood and cerebrospinal fluid for neuropathic pain in different neuropathies. METHODS: Searches were performed in six databases: PubMed, Web of Science, Scopus, Cochrane Library, EMBASE, and CINAHL. Included were observational studies, namely cross-sectional, cohort, and case-control, that evaluated quantitative biomarkers in blood or cerebrospinal fluid. Data were qualitatively synthesized, and meta-analyses were conducted using R. The study is registered with PROSPERO under the ID CRD42022323769. RESULTS: The literature search resulted in 16 studies for qualitative and 12 for quantitative analysis, covering patients over 18 years of age with painful neuropathies. A total of 1403 subjects were analyzed, identifying no significant differences in levels of C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-alpha) between patients with and without pain. Despite the high inter-rater reliability and adequate bias assessment, the results suggest negligible differences in inflammatory biomarkers, with noted publication bias and heterogeneity among studies, indicating the need for further research. CONCLUSIONS: Our review underscores the complex nature of neuropathic pain and the challenges in identifying biomarkers, with no significant differences found in CRP, IL-6, and TNF-alpha levels between patients with and without pain. Despite methodological robustness, the results are limited by publication bias and heterogeneity. This emphasizes the need for further research to discover definitive biomarkers for improved diagnosis and personalized treatment of neuropathic pain.

Exploring novel dilazep derivatives as hENT1 inhibitors and potentially covalent molecular tools.

The human equilibrative nucleoside transporter 1 (SLC29A1, hENT1) is a solute carrier that modulates the passive transport of nucleosides and nucleobases, such as adenosine. This nucleoside regulates various physiological processes, such as vasodilation and -constriction, neurotransmission and immune defense. Marketed drugs such as dilazep and dipyridamole have proven useful in cardiovascular afflictions, but the application of hENT1 inhibitors can be beneficial in a number of other diseases. In this study, 39 derivatives of dilazep's close analogue ST7092 were designed, synthesized and subsequently assessed using [3H]NBTI displacement assays and molecular docking. Different substitution patterns of the trimethoxy benzoates of ST7092 reduced interactions within the binding pocket, resulting in diminished hENT1 affinity. Conversely, [3H]NBTI displacement by potentially covalent compounds 14b, 14c, and 14d resulted in high affinities (Ki values between 1.1 and 17.5 nM) for the transporter, primarily by the ability of accommodating the inhibitors in various ways in the binding pocket. However, any indication of covalent binding with amino acid residue C439 remained absent, conceivably as a result of decreased nucleophilic residue reactivity. In conclusion, this research introduces novel dilazep derivatives that are active as hENT1 inhibitors, along with the first high affinity dilazep derivatives equipped with an electrophilic warhead. These findings will aid the rational and structure-based development of novel hENT1 inhibitors and pharmacological tools to study hENT1's function, binding mechanisms, and its relevance in (patho)physiological conditions.

Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities.

Cancer remains a leading cause of mortality worldwide and calls for novel therapeutic targets. Membrane proteins are key players in various cancer types but present unique challenges compared to soluble proteins. The advent of computational drug discovery tools offers a promising approach to address these challenges, allowing for the prioritization of "wet-lab" experiments. In this review, we explore the applications of computational approaches in membrane protein oncological characterization, particularly focusing on three prominent membrane protein families: receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and solute carrier proteins (SLCs). We chose these families due to their varying levels of understanding and research data availability, which leads to distinct challenges and opportunities for computational analysis. We discuss the utilization of multi-omics data, machine learning, and structure-based methods to investigate aberrant protein functionalities associated with cancer progression within each family. Moreover, we highlight the importance of considering the broader cellular context and, in particular, cross-talk between proteins. Despite existing challenges, computational tools hold promise in dissecting membrane protein dysregulation in cancer. With advancing computational capabilities and data resources, these tools are poised to play a pivotal role in identifying and prioritizing membrane proteins as personalized anticancer targets.

Still in Search for an EAAT Activator: GT949 Does Not Activate EAAT2, nor EAAT3 in Impedance and Radioligand Uptake Assays.

Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain scarce. Recently, GT949 was proposed as a selective activator of EAAT2, as tested in a radioligand uptake assay. In the presented research, we aimed to validate the use of GT949 to activate EAAT2-driven glutamate transport by applying an innovative, impedance-based, whole-cell assay (xCELLigence). A broad range of GT949 concentrations in a variety of cellular environments were tested in this assay. As expected, no activation of EAAT3 could be detected. Yet, surprisingly, no biological activation of GT949 on EAAT2 could be observed in this assay either. To validate whether the impedance-based assay was not suited to pick up increased glutamate uptake or if the compound might not induce activation in this setup, we performed radioligand uptake assays. Two setups were utilized; a novel method compared to previously published research, and in a reproducible fashion copying the methods used in the existing literature. Nonetheless, activation of neither EAAT2 nor EAAT3 could be observed in these assays. Furthermore, no evidence of GT949 binding or stabilization of purified EAAT2 could be observed in a thermal shift assay. To conclude, based on experimental evidence in the present study GT949 requires specific assay conditions, which are difficult to reproduce, and the compound cannot simply be classified as an activator of EAAT2 based on the presented evidence. Hence, further research is required to develop the tools needed to identify new EAAT modulators and use their potential as a therapeutic target.

MicroRNAs as Potential Graft Rejection or Tolerance Biomarkers and Their Dilemma in Clinical Routines Behaving like Devilish, Angelic, or Frightening Elements.

Allograft rejection is a widespread complication in allograft recipients with chronic kidney disease. Undertreatment of subclinical and clinical rejection and later post-transplant problems are caused by an imperfect understanding of the mechanisms at play and a lack of adequate diagnostic tools. Many different biomarkers have been analyzed and proposed to detect and monitor these crucial events in transplant outcomes. In this sense, microRNAs may help diagnose rejection or tolerance and indicate appropriate treatment, especially in patients with chronic allograft rejection. As key epigenetic regulators of physiological homeostasis, microRNAs have therapeutic potential and may indicate allograft tolerance or rejection. However, more evidence and clinical validation are indispensable before microRNAs are ready for clinical prime time.

Molecular insights into disease-associated glutamate transporter (EAAT1 / SLC1A3) variants using in silico and in vitro approaches.

Glutamate is an essential excitatory neurotransmitter and an intermediate for energy metabolism. Depending on the tumor site, cancer cells have increased or decreased expression of excitatory amino acid transporter 1 or 2 (EAAT1/2, SLC1A3/2) to regulate glutamate uptake for the benefit of tumor growth. Thus, EAAT1/2 may be an attractive target for therapeutic intervention in oncology. Genetic variation of EAAT1 has been associated with rare cases of episodic ataxia, but the occurrence and functional contribution of EAAT1 mutants in other diseases, such as cancer, is poorly understood. Here, 105 unique somatic EAAT1 mutations were identified in cancer patients from the Genomic Data Commons dataset. Using EAAT1 crystal structures and in silico studies, eight mutations were selected based on their close proximity to the orthosteric or allosteric ligand binding sites and the predicted change in ligand binding affinity. In vitro functional assessment in a live-cell, impedance-based phenotypic assay demonstrated that these mutants differentially affect L-glutamate and L-aspartate transport, as well as the inhibitory potency of an orthosteric (TFB-TBOA) and allosteric (UCPH-101) inhibitor. Moreover, two episodic ataxia-related mutants displayed functional responses that were in line with literature, which confirmed the validity of our assay. Of note, ataxia-related mutant M128R displayed inhibitor-induced functional responses never described before. Finally, molecular dynamics (MD) simulations were performed to gain mechanistic insights into the observed functional effects. Taken together, the results in this work demonstrate 1) the suitability of the label-free phenotypic method to assess functional variation of EAAT1 mutants and 2) the opportunity and challenges of using in silico techniques to rationalize the in vitro phenotype of disease-relevant mutants.

Innovación tecnológica frente a la expiración de patentes farmacéuticas: el nacimiento de las terapias digitales / [Technological innovation in the face of the expiration of pharmaceutical patents: the birth of digital therapies]

La expiración de patentes farmacéuticas sobre medicamentos favorece la realización de prácticas comerciales dentro del sector que obstaculizan la entrada de los medicamentos genéricos. La creación de terapias digitales a través de la incorporación de componentes digitales en productos farmacéuticos tradicionales es una alternativa innovadora que combina la aportación de un valor añadido a un producto farmacéutico obsoleto a la vez que aborda problemas sanitarios serios de forma transformadora. Este tipo de prácticas podría ayudar a las empresas farmacéuticas a mantener su hueco de mercado tras la expiración de la patente de un medicamento superventas. (AU)

The expiry of pharmaceutical patents on medical products encourages commercial practices within the sector that hinder the entry of generic medicines. The creation of digital therapies through the incorporation of digital components into traditional pharmaceuticals is an innovative alternative that combines adding value to an obsolete pharmaceutical product while addressing serious health problems in a transformative way. Such practices could help pharmaceutical companies to maintain their market niche after the patent expiry of a blockbuster drug. (AU)

Simultaneous diagnosis of well-differentiated neuroendocrine tumour and gastrointestinal stromal tumour of the stomach: an infrequent finding.

We present the case of a 75-year-old female patient who was referred to gastroenterology consultation due to vitamin B12 deficiency. Anti-parietal cell and anti-intrinsic factor antibodies were positive. An upper gastrointestinal endoscopy was performed for the suspicion of autoimmune gastritis, identifying in the greater curvature of the gastric corpus a 25 mm spherical, subepithelial lesion, suggestive of gastrointestinal stromal tumour (GIST). A 2 mm sessile polyp was observed adjacent to it. Biopsies from both lesions were taken. Histological examination of the submucosal lesion showed mucosa with neuroendocrine cell dysplasia. The polypoid lesion was compatible with a well-differentiated neuroendocrine tumour (G1) with affected margins. A SPECT-CT scan was performed, showing the lesion compatible with GIST expression of somatostatin receptors. There were no signs of distant extension. Using endoscopic ultrasound, the subepithelial lesion was described as a hypoechoic bulge of the fourth layer, measuring 25 x 18 mm. It was not possible to visualize the polyp. EUS-guided fine needle aspiration was performed, and cytology was negative for malignancy. Finally, it was decided to perform an atypical, laparoscopic gastric greater curvature resection. Neuroendocrine tumours (NETs) are epithelial neoplasms derived from cells of the diffuse neuroendocrine system. Gastrointestinal stromal tumours (GISTs), although they represent 1-3% of gastrointestinal neoplasms, are the most common mesenchymal tumours, arising from interstitial Cajal cells. The synchronous finding in the stomach of a well-differentiated NET and a GIST is rare, having been described in a low percentage of cases.

Artificial intelligence for natural product drug discovery.

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to exciting developments in the computational drug design field, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature. We also discuss how to address key challenges in realizing the potential of these synergies, such as the need for high-quality datasets to train deep learning algorithms and appropriate strategies for algorithm validation.

Human genetic adaptation related to cellular zinc homeostasis.

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.

3DDPDs: describing protein dynamics for proteochemometric bioactivity prediction. A case for (mutant) G protein-coupled receptors.

Proteochemometric (PCM) modelling is a powerful computational drug discovery tool used in bioactivity prediction of potential drug candidates relying on both chemical and protein information. In PCM features are computed to describe small molecules and proteins, which directly impact the quality of the predictive models. State-of-the-art protein descriptors, however, are calculated from the protein sequence and neglect the dynamic nature of proteins. This dynamic nature can be computationally simulated with molecular dynamics (MD). Here, novel 3D dynamic protein descriptors (3DDPDs) were designed to be applied in bioactivity prediction tasks with PCM models. As a test case, publicly available G protein-coupled receptor (GPCR) MD data from GPCRmd was used. GPCRs are membrane-bound proteins, which are activated by hormones and neurotransmitters, and constitute an important target family for drug discovery. GPCRs exist in different conformational states that allow the transmission of diverse signals and that can be modified by ligand interactions, among other factors. To translate the MD-encoded protein dynamics two types of 3DDPDs were considered: one-hot encoded residue-specific (rs) and embedding-like protein-specific (ps) 3DDPDs. The descriptors were developed by calculating distributions of trajectory coordinates and partial charges, applying dimensionality reduction, and subsequently condensing them into vectors per residue or protein, respectively. 3DDPDs were benchmarked on several PCM tasks against state-of-the-art non-dynamic protein descriptors. Our rs- and ps3DDPDs outperformed non-dynamic descriptors in regression tasks using a temporal split and showed comparable performance with a random split and in all classification tasks. Combinations of non-dynamic descriptors with 3DDPDs did not result in increased performance. Finally, the power of 3DDPDs to capture dynamic fluctuations in mutant GPCRs was explored. The results presented here show the potential of including protein dynamic information on machine learning tasks, specifically bioactivity prediction, and open opportunities for applications in drug discovery, including oncology.

All That Glitters in cfDNA Analysis Is Not Gold or Its Utility Is Completely Established Due to Graft Damage: A Critical Review in the Field of Transplantation.

In kidney transplantation, a biopsy is currently the gold standard for monitoring the transplanted organ. However, this is far from an ideal screening method given its invasive nature and the discomfort it can cause the patient. Large-scale studies in renal transplantation show that approximately 1% of biopsies generate major complications, with a risk of macroscopic hematuria greater than 3.5%. It would not be until 2011 that a method to detect donor-derived cell-free DNA (dd-cfDNA) employing digital PCR was devised based on analyzing the differences in SNPs between the donor and recipient. In addition, since the initial validation studies were carried out at the specific moments in which rejection was suspected, there is still not a good understanding of how dd-cfDNA levels naturally evolve post-transplant. In addition, various factors, both in the recipient and the donor, can influence dd-cfDNA levels and cause increases in the levels of dd-cfDNA themselves without suspicion of rejection. All that glitters in this technology is not gold; therefore, in this article, we discuss the current state of clinical studies, the benefits, and disadvantages.

Social Media, Anxiety and COVID-19 Lockdown Measurement Compliance.

The aim of the present research was to analyze the effect of anxiety levels during the COVID-19 pandemic in the use of social media and compliance with lockdown measures during the confinement. A total of 1723 participants (32.1% males and 77.9% females; 32.6 ± 9.2 years) were interviewed by a Spanish version of the Spielberger State-Trait Anxiety Inventory. From the results obtained, the sample was divided into two 50th percentile groups, a high anxiety group (HAG) and a low anxiety group (LAG). We found how the LAG had lower use of social networks such as Facebook and Twitter during confinement. Also, this group presented a higher rate of leaving home during the confinement and higher values in people with whom they had lived with during confinement than high anxiety group. Regardless of the lack of results in the remaining variables, the present study nuances the high levels of anxiety experienced during COVID-19 confinement. The multifactorial analysis of factors related to the perception of anxiety during COVID-19 confinement may be a useful tool to measure multiple social behaviors when examining mental health factors. Thus, explaining and preventing the psychological consequences of the COVID-19 pandemic. The present knowledge could be used to determine key intervention factors for reducing the perception of fear and anxiety.

Irregular ventricular tachycardia originating from the moderator band.

Ventricular tachycardias (VT) may initially show beat to beat oscillations but rapidly stabilize into a regular tachycardia with a stable cycle length. A persistently irregular ventricular tachycardia is a rare phenomenon. We report a rare case of an "irregular" ventricular tachycardia with so pronounced oscillations in cycle length that it was initially misdiagnosed as atrial fibrillation with aberrant conduction. This ventricular tachycardia was incessant and resulted in a tachycardia induced cardiomyopathy refractory to several antiarrhythmic drugs. Mapping of the right ventricle demonstrated that the tachycardia had a focal origin in the moderator band close to its insertion into the anterior papillary muscle. Radiofrequency ablation eliminated the tachycardia with eventual normalization of left ventricular function. The moderator band and anterior papillary muscle of the right ventricle are known to be the source of short-coupled ventricular premature beats and regular ventricular tachycardias. However, an "irregular" ventricular tachycardia has not been previously reported to arise from these structures.

Medicago sativa L. Plant Response against Possible Eustressors (Fe, Ag, Cu)-TiO2: Evaluation of Physiological Parameters, Total Phenol Content, and Flavonoid Quantification.

The present study analyzed Medicago sativa L. crops irrigated by TiO2 in the anatase phase and TiO2 doped with Ag, Fe, and Cu ions at 0.1%w synthesized using the sol-gel method (SG) and the sol-gel method coupled with microwave (Mw-SG). The materials were added to the irrigation water at different concentrations (50, 100, and 500 ppm). Stress induction by nanomaterials was observed by measuring stem morphology, chlorophyll index, total phenols and flavonoids, and antioxidant activity through the DPPH (2,2-diphenyl-1-picrylhydrazy) radical inhibition assay. The nanomaterial treatments caused statistically significant reductions in parameters such as stem length, leaf size, and chlorophyll index and increases in total phenol content and DPPH inhibition percentage. However, the observed effects did not show clear evidence regarding the type of nanomaterial used, its synthesis methodology, or a concentration-dependent response. By generally grouping the results obtained to the type of dopant used and the synthesis method, the relationship between them was determined employing a two-way ANOVA. It was observed that the dopant factors, synthesis, and interaction were relevant for most treatments. Additionally, the addition of microwaves in the synthesis method resulted in the largest number of treatments with a significant increase in the total content of phenols and the % inhibition compared to the traditional sol-gel synthesis. In contrast, parameters such as stem size and chlorophyll index were affected under different treatments from both synthesis methods.

Adaptation of Venezuelan refugees in Colombia: The mediating roles of acculturation orientations in influencing acculturation adaptations.

As of 2021, over 5.4 million Venezuelans have fled their home country in search of safety, food, medicine and access to essential services. This is the most substantial exodus in the recent history of Latin America. Colombia has received 2 million of these refugees, making it the nation host to the greatest number of Venezuelan refugees. The present research aims to examine the relations between the sociocultural and psychological factors that are associated with Psychological Adaptation of Venezuelan refugees living in Colombia. We also examined how these relations were mediated by the acculturation orientations. Among Venezuelan refugees, higher Psychological Strength, lower Perceived Discrimination, higher National Identity and higher Outgroup Social Support, were significantly associated with higher engagement with Colombian society and better Psychological Adaptation. Orientation to the host (Colombian) society mediated the association between (a) National Identity and Psychological Adaptation, (b) Outgroup Social Support and Psychological Adaptation and (c) Perceived Discrimination and Psychological Adaptation. The results may inform refugee receiving societies of some essential factors and positive strategies behind adaptation of refugees.