Gamification and Oral Health in Children and Adolescents: Scoping Review.

BACKGROUND: Oral health is a determinant of overall well-being and quality of life. Individual behaviors, such as oral hygiene and dietary habits, play a central role in oral health. Motivation is a crucial factor in promoting behavior change, and gamification offers a means to boost health-related knowledge and encourage positive health behaviors. OBJECTIVE: This study aims to evaluate the impact of gamification and its mechanisms on oral health care of children and adolescents. METHODS: A systematic search covered multiple databases: PubMed/MEDLINE, PsycINFO, the Cochrane Library, ScienceDirect, and LILACS. Gray literature, conference proceedings, and WHOQOL internet resources were considered. Studies from January 2013 to December 2022 were included, except for PubMed/MEDLINE, which was searched until January 2023. A total of 15 studies were selected following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The eligibility criteria were peer-reviewed, full-text, and empirical research related to gamification in oral health care, reports of impact, and oral health care outcomes. The exclusion criteria encompassed duplicate articles; unavailable full texts; nonoriginal articles; and non-digital game-related, non-oral health-related, and protocol studies. Selected studies were scrutinized for gamification mechanisms and outcomes. Two main questions were raised: "Does gamification in oral health care impact oral health?" and "Does oral health care gamification enhance health promotion and literacy?" The PICO (Patient, Intervention, Comparison, Outcome) framework guided the scoping review. RESULTS: Initially, 617 records were obtained from 5 databases and gray literature sources. After applying exclusion criteria, 15 records were selected. Sample size in the selected studies ranged from 34 to 190 children and adolescents. A substantial portion (11/15, 73%) of the studies discussed oral self-care apps supported by evidence-based oral health. The most clearly defined data in the apps were "brushing time" (11/11, 100%) and "daily amount brushing" (10/11, 91%). Most studies (11/15, 73%) mentioned oral health care behavior change techniques and included "prompt intention formation" (11/26, 42%), "providing instructions" (11/26, 42%), "providing information on the behavior-health link" (10/26, 38%), "providing information on consequences" (9/26, 35%), "modeling or demonstrating behavior" (9/26, 35%), "providing feedback on performance" (8/26, 31%), and "providing contingent rewards" (8/26, 31%). Furthermore, 80% (12/15) of the studies identified game design elements incorporating gamification features in oral hygiene applications. The most prevalent gamification features were "ideological incentives" (10/12, 83%) and "goals" (9/16, 56%), which were found in user-specific and challenge categories, respectively. CONCLUSIONS: Gamification in oral health care shows potential as an innovative approach to promote positive health behaviors. Most studies reported evidence-based oral health and incorporated oral health care behavior change techniques.

An Efficient Edge Computing-Enabled Network for Used Cooking Oil Collection.

In Portugal, more than 98% of domestic cooking oil is disposed of improperly every day. This avoids recycling/reconverting into another energy. Is also may become a potential harmful contaminant of soil and water. Driven by the utility of recycled cooking oil, and leveraging the exponential growth of ubiquitous computing approaches, we propose an IoT smart solution for domestic used cooking oil (UCO) collection bins. We call this approach SWAN, which stands for Smart Waste Accumulation Network. It is deployed and evaluated in Portugal. It consists of a countrywide network of collection bin units, available in public areas. Two metrics are considered to evaluate the system's success: (i) user engagement, and (ii) used cooking oil collection efficiency. The presented system should (i) perform under scenarios of temporary communication network failures, and (ii) be scalable to accommodate an ever-growing number of installed collection units. Thus, we choose a disruptive approach from the traditional cloud computing paradigm. It relies on edge node infrastructure to process, store, and act upon the locally collected data. The communication appears as a delay-tolerant task, i.e., an edge computing solution. We conduct a comparative analysis revealing the benefits of the edge computing enabled collection bin vs. a cloud computing solution. The studied period considers four years of collected data. An exponential increase in the amount of used cooking oil collected is identified, with the developed solution being responsible for surpassing the national collection totals of previous years. During the same period, we also improved the collection process as we were able to more accurately estimate the optimal collection and system's maintenance intervals.

Innovative flow-through reaction system for the sustainable production of phenolic monomers from lignocellulose catalyzed by supported Mo2C.

Molybdenum carbide supported on activated carbon (ß-Mo2C/AC) has been tested as catalyst in the reductive catalytic fractionation (RCF) of lignocellulosic biomass both in batch and in Flow-Through (FT) reaction systems. High phenolic monomer yields (34 wt.%) and selectivity to monomers with reduced side alkyl chains (up to 80 wt.%) could be achieved in batch in the presence of hydrogen. FT-RCF were made with no hydrogen feed, thus via transfer hydrogenation from ethanol. Similar selectivity could be attained in FT-RCF using high catalyst/biomass ratios (0.6) and high molybdenum loading (35 wt.%) in the catalyst, although selectivity decreased with lower catalyst/biomass ratios or molybdenum contents. Regardless of these parameters, high delignification of the lignocellulosic biomass and similar monomer yields were observed in the FT mode (13-15 wt.%) while preserving the holocellulose fractions in the delignified pulp. FT-RCF system outperforms the batch reaction mode in the absence of hydrogen, both in terms of activity and selectivity to reduced monomers that is attributed to the two-step non-equilibrium processes and the removal of diffusional limitations that occur in the FT mode. Even though some molybdenum leaching was detected, the catalytic performance could be maintained with negligible loss of activity or selectivity for 15 consecutive runs.

New azaaurone derivatives as potential multitarget agents in HIV-TB coinfection.

Tuberculosis (TB) disease, caused by Mycobacterium tuberculosis (Mtb) is the leading cause of death among people with human immunodeficiency virus (HIV) infection. No dual-target drug is currently being used to simultaneously treat both infections. This work aimed to obtain new multitarget HIV-TB agents, with the goal of optimizing treatments and preventing this coinfection. These compounds incorporate the structural features of azaaurones as anti-Mtb and zidovudine (AZT) as the antiretroviral moiety. The azaaurone scaffold displayed submicromolar activities against Mtb, and AZT is a potent antiretroviral drug. Six derivatives were synthetically generated, and five were evaluated against both infective agents. Evaluations of anti-HIV activity were carried out in HIV-1-infected MT-4 cells and on endogenous HIV-1 reverse transcriptase (RT) activity. The H37Rv strain was used for anti-Mtb assessments. Most compounds displayed potent antitubercular and moderate anti-HIV activity. (E)-12 exhibited a promising multitarget profile with an MIC90 of 2.82 µM and an IC50 of 1.98 µM in HIV-1-infected T lymphocyte cells, with an 84% inhibition of RT activity. Therefore, (E)-12 could be the first promising compound from a family of multitarget agents used to treat HIV-TB coinfection. In addition, the compound could offer a prototype for the development of new strategies in scientific research to treat this global health issue.

Chronic gastric volvulus with diaphragmatic eventration: Case presentation.

INTRODUCTION AND IMPORTANCE: Gastric volvulus is a rare clinical entity which occurs due to the rotation of the stomach and can have life-threatening complications. This condition can have an acute or chronic presentation and its symptoms will vary according to the degree of obstruction and rapidity of onset. CASE PRESENTATION: We report a case of a 84-year-old male with history of frequent periods of constipation and lack of appetite who presented to the emergency room with left-sided abdominal pain and distension and persistent nausea, without the ability to vomit. Abdominal radiograph, computed tomography scan of the abdomen, contrast-enhanced examination and upper endoscopy were consistent with a gastric volvulus secondary to diaphragmatic eventration. The patient's symptoms resolved after nasogastric tube placement and fluid resuscitation. However, he was proposed to a laparoscopic anterior gastropexy to prevent symptom recurrence. He remains asymptomatic after 3 years of follow-up. CLINICAL DISCUSSION: The diagnosis of gastric volvulus is based mainly on clinical presentation and abdominal imaging. The main principles of surgical intervention include stomach decompression with volvulus reduction, followed by gastropexy and correction of any predisposing intra-abdominal factors. CONCLUSION: Definitive treatment of both acute and chronic gastric volvulus includes a surgical approach. Laparoscopic anterior gastropexy has been found to be a viable alternative in these patients.

Structural Optimization of Antimycobacterial Azaaurones Towards Improved Solubility and Metabolic Stability.

While N-acetyl azaaurones have already been disclosed for their potential against tuberculosis (TB), their low metabolic stability remains an unaddressed liability. We now report a study designed to improve the metabolic stability and solubility of the azaaurone scaffold and to identify the structural requirements for antimycobacterial activity. Replacing the N-acetyl moiety for a N-carbamoyl group led to analogues with sub- and nanomolar potencies against M. tuberculosis H37Rv, as well as equipotent against drug-susceptible and drug-resistant M. tuberculosis isolates. The new N-carbamoyl azaaurones exhibited improved microsomal stability, compared to their N-acetylated counterparts, with several compounds displaying moderate to high kinetic solubility. The frequency of spontaneous resistance to azaaurones was observed to be in the range of 10-8 , a value that is comparable to current TB drugs in the market. Overall, these results reveal that azaaurones are amenable to structural modifications to improve metabolic and solubility liabilities, and highlight their potential as antimycobacterial agents.

4-Oxo-ß-Lactams as Novel Inhibitors for Rhomboid Proteases.

Intramembrane serine proteases (rhomboid proteases) are involved in a variety of biological processes and are implicated in several diseases. Here, we report 4-oxo-ß-lactams as a novel scaffold for inhibition of rhomboids. We show that they covalently react with the active site and that the covalent bond is sufficiently stable for detection of the covalent rhomboid-lactam complex. 4-Oxo-ß-lactams may therefore find future use as both inhibitors and activity-based probes for rhomboid proteases.

Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach.

A multistep and diversity-oriented synthetic route aiming at the A3 coupling/domino cyclization of o-ethynyl anilines, aldehydes and s-amines is described. The preparation of the corresponding precursors included a series of transformations, such as haloperoxidation and Sonogashira cross-coupling reactions, amine protection, desilylation and amine reduction. Some products of the multicomponent reaction underwent further detosylation and Suzuki coupling. The resulting library of structurally diverse compounds was evaluated against blood and liver stage malaria parasites, which revealed a promising lead with sub-micromolar activity against intra-erythrocytic forms of Plasmodium falciparum. The results from this hit-to-lead optimization are hereby reported for the first time.

Spontaneous retroperitoneal biloma in a patient with choledocholithiasis: Presentation of case.

INTRODUCTION AND IMPORTANCE: Spontaneous perforation of the biliary tree, resulting in retroperitoneal biloma in adults is an extremely rare condition, and may unfold to a potentially fatal outcome, particularly when the diagnosis and definitive treatment are delayed. CASE PRESENTATION: We report a case of a 69-year-old male who presented to the emergency room with abdominal pain, localized to the right quadrants, associated with jaundice and dark-coloured urine. Abdominal imaging including CT scan, ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed a retroperitoneal fluid collection, a distended gallbladder with wall thickening and lithiasis, as well as a dilated common bile duct (CBD) with choledocholithiasis. The analysis of the retroperitoneal fluid obtained by CT-guided percutaneous drainage was consistent with biloma. A combined approach of biloma percutaneous drainage and endoscopic retrograde cholangiopancreatography (ERCP)-guided stent placement in the CBD with biliary stones removal was successful in the management of this patient, despite the fact that the perforation site could not be detected. CLINICAL DISCUSSION: The diagnosis of biloma is based mainly on clinical presentation and abdominal imaging. If urgent surgical intervention is not indicated, pressure necrosis and perforation of the biliary tree may be avoided by timely percutaneous aspiration of the biloma and ERCP to remove the impacted stones in the biliary tree. CONCLUSION: Biloma should be considered in the differential diagnosis of a patient presenting with right upper quadrant or epigastric pain and an intra-abdominal collection on imaging. Efforts should be made in order to offer a prompt diagnosis and treatment to the patient.

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens.

The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient's immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and Mycobacterium tuberculosis (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.

Polysulfone Membranes Doped with Human Neutrophil Elastase Inhibitors: Assessment of Bioactivity and Biocompatibility.

The use of polysulfone (PSU) hemodialysis (HD) membranes modified with bioactive compounds has gained relevance in chronic kidney disease (CKD) management. Compounds based on the 4-oxo-ß-lactam scaffold have outstanding inhibitory ability and selectivity for human neutrophil elastase (HNE). The present work aimed to evaluate the bioactivity and biocompatibility of PSU-based HD membranes doped with HNE inhibitors (HNEIs). For this, two 4-oxo-ß-lactam derivates (D4L-1 and D4L-2) synthesized in house were used, as well as a commercial HNEI (Sivelestat), for comparison purposes. Their HNE inhibition efficacy was evaluated in in vitro and ex vivo (incubations with human plasma) assay conditions. All biomaterials were bioactive and hemocompatible. The inhibitory capacity of the HNEIs and HNEI-PSU membranes in vitro was D4L-1 > D4L-2 > Sivelestat and D4L-2 > Sivelestat > D4L-1, respectively. In ex vivo conditions, both HNEIs and HNEI-PSU materials presented the same relative inhibitory ability (D4L-1 > D4L-2 > Sivelestat). The difference observed between in vitro and ex vivo conditions is most likely due to the inherent lipophilicity/hydrophobicity of each HNEI influencing their affinity and accessibility to HNE when trapped in the membrane. Compared to Sivelestat, both D4L-1 and D4L-2 (and the respective doped membranes) have more potent inhibition capabilities. In conclusion, this work reports the successful development of PSU membranes functionalized with HNEIs.

The Facets of Diversity: The EFMC Perspective.

Diversity in science refers to cultivating talent, while promoting full inclusion across the community. In medicinal chemistry and chemical biology, it enhances creativity and encourages contributions from multiple perspectives, leading to better decision making and broader scientific impact. The European Federation for Medicinal chemistry and Chemical biology (EFMC) embraces and promotes diversity, to ensure representation of all talents, and enable equality of opportunity through fairness and transparency. EFMC has historically paid continuous attention to diversity in terms of culture, geography and equilibrium between academia and industry, with over the last few years a focus on increasing gender balance, aiming at a fair representation of the scientific community and equal opportunities independently of gender. EFMC promotes cultural diversity as it reinforces openness and mutual respect. All scientific organizations of a scope compatible with its remit are welcome within EFMC, where their members benefit from a welcoming, psychologically safe, and stimulating environment. Herein, we describe the state of diversity within the EFMC, how the situation has evolved over the years and where diversity should be further encouraged.

SchoolAIR: A Citizen Science IoT Framework Using Low-Cost Sensing for Indoor Air Quality Management.

Indoor air quality (IAQ) problems in school environments are very common and have significant impacts on students' performance, development and health. Indoor air conditions depend on the adopted ventilation practices, which in Mediterranean countries are essentially based on natural ventilation controlled through manual window opening. Citizen science projects directed to school communities are effective strategies to promote awareness and knowledge acquirement on IAQ and adequate ventilation management. Our multidisciplinary research team has developed a framework-SchoolAIR-based on low-cost sensors and a scalable IoT system architecture to support the improvement of IAQ in schools. The SchoolAIR framework is based on do-it-yourself sensors that continuously monitor air temperature, relative humidity, concentrations of carbon dioxide and particulate matter in school environments. The framework was tested in the classrooms of University Fernando Pessoa, and its deployment and proof of concept took place in a high school in the north of Portugal. The results obtained reveal that CO2 concentrations frequently exceed reference values during classes, and that higher concentrations of particulate matter in the outdoor air affect IAQ. These results highlight the importance of real-time monitoring of IAQ and outdoor air pollution levels to support decision-making in ventilation management and assure adequate IAQ. The proposed approach encourages the transfer of scientific knowledge from universities to society in a dynamic and active process of social responsibility based on a citizen science approach, promoting scientific literacy of the younger generation and enhancing healthier, resilient and sustainable indoor environments.

Chemoproteomics-Enabled Identification of 4-Oxo-ß-Lactams as Inhibitors of Dipeptidyl Peptidases 8 and 9.

Dipeptidyl peptidases 8 and 9 (DPP8/9) have gathered interest as drug targets due to their important roles in biological processes like immunity and tumorigenesis. Elucidation of their distinct individual functions remains an ongoing task and could benefit from the availability of novel, chemically diverse and selective chemical tools. Here, we report the activity-based protein profiling (ABPP)-mediated discovery of 4-oxo-ß-lactams as potent, non-substrate-like nanomolar DPP8/9 inhibitors. X-ray crystallographic structures revealed different ligand binding modes for DPP8 and DPP9, including an unprecedented targeting of an extended S2' (eS2') subsite in DPP8. Biological assays confirmed inhibition at both target and cellular levels. Altogether, our integrated chemical proteomics and structure-guided small molecule design approach led to novel DPP8/9 inhibitors with alternative molecular inhibition mechanisms, delivering the highest selectivity index reported to date.

Discovery of XL01126: A Potent, Fast, Cooperative, Selective, Orally Bioavailable, and Blood-Brain Barrier Penetrant PROTAC Degrader of Leucine-Rich Repeat Kinase 2.

Leucine-rich repeat kinase 2 (LRRK2) is one of the most promising targets for Parkinson's disease. LRRK2-targeting strategies have primarily focused on type 1 kinase inhibitors, which, however, have limitations as the inhibited protein can interfere with natural mechanisms, which could lead to undesirable side effects. Herein, we report the development of LRRK2 proteolysis targeting chimeras (PROTACs), culminating in the discovery of degrader XL01126, as an alternative LRRK2-targeting strategy. Initial designs and screens of PROTACs based on ligands for E3 ligases von Hippel-Lindau (VHL), Cereblon (CRBN), and cellular inhibitor of apoptosis (cIAP) identified the best degraders containing thioether-conjugated VHL ligand VH101. A second round of medicinal chemistry exploration led to qualifying XL01126 as a fast and potent degrader of LRRK2 in multiple cell lines, with DC50 values within 15-72 nM, Dmax values ranging from 82 to 90%, and degradation half-lives spanning from 0.6 to 2.4 h. XL01126 exhibits high cell permeability and forms a positively cooperative ternary complex with VHL and LRRK2 (α = 5.7), which compensates for a substantial loss of binary binding affinities to VHL and LRRK2, underscoring its strong degradation performance in cells. Remarkably, XL01126 is orally bioavailable (F = 15%) and can penetrate the blood-brain barrier after either oral or parenteral dosing in mice. Taken together, these experiments qualify XL01126 as a suitable degrader probe to study the noncatalytic and scaffolding functions of LRRK2 in vitro and in vivo and offer an attractive starting point for future drug development.

Harnessing Protein-Ligand Interaction Fingerprints to Predict New Scaffolds of RIPK1 Inhibitors.

Necroptosis has emerged as an exciting target in oncological, inflammatory, neurodegenerative, and autoimmune diseases, in addition to acute ischemic injuries. It is known to play a role in innate immune response, as well as in antiviral cellular response. Here we devised a concerted in silico and experimental framework to identify novel RIPK1 inhibitors, a key necroptosis factor. We propose the first in silico model for the prediction of new RIPK1 inhibitor scaffolds by combining docking and machine learning methodologies. Through the data analysis of patterns in docking results, we derived two rules, where rule #1 consisted of a four-residue signature filter, and rule #2 consisted of a six-residue similarity filter based on docking calculations. These were used in consensus with a machine learning QSAR model from data collated from ChEMBL, the literature, in patents, and from PubChem data. The models allowed for good prediction of actives of >90, 92, and 96.4% precision, respectively. As a proof-of-concept, we selected 50 compounds from the ChemBridge database, using a consensus of both molecular docking and machine learning methods, and tested them in a phenotypic necroptosis assay and a biochemical RIPK1 inhibition assay. A total of 7 of the 47 tested compounds demonstrated around 20−25% inhibition of RIPK1's kinase activity but, more importantly, these compounds were discovered to occupy new areas of chemical space. Although no strong actives were found, they could be candidates for further optimization, particularly because they have new scaffolds. In conclusion, this screening method may prove valuable for future screening efforts as it allows for the exploration of new areas of the chemical space in a very fast and inexpensive manner, therefore providing efficient starting points amenable to further hit-optimization campaigns.

Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones Active against Plasmodium and Trypanosomatids.

Malaria, leishmaniasis, and sleeping sickness are potentially fatal diseases that represent a real health risk for more than 3,5 billion people. New antiparasitic compounds are urgent leading to a constant search for novel scaffolds. Herein, pyrazino[2,1-b]quinazoline-3,6-diones containing indole alkaloids were explored for their antiparasitic potential against Plasmodium falciparum, Trypanosoma brucei, and Leishmania infantum. The synthetic libraries furnished promising hit compounds that are species specific (7, 12) or with broad antiparasitic activity (8). Structure-activity relationships were more evident for Plasmodium with anti-isomers (1S,4R) possessing excellent antimalarial activity, while the presence of a substituent on the anthranilic acid moiety had a negative effect on the activity. Hit compounds against malaria did not inhibit ß-hematin, and in silico studies predicted these molecules as possible inhibitors for prolyl-tRNA synthetase both from Plasmodium and Leishmania. These results disclosed a potential new chemotype for further optimization toward novel and affordable antiparasitic drugs.

Tandem Thio-Michael Addition/Remote Lactone Activation of 5-Hydroxymethylfurfural-Derived δ-Lactone-Fused Cyclopentenones.

The creation of structurally diverse chemical entities from fairly simple biorefinery products remains a challenge. In this work 5-hydroxymethylfurfural (HMF) was identified as a key synthon for preparing highly complex cyclopentenones (CP) via tandem 1,4-addition/elimination/remote lactone activation to external O- and N-nucleophiles in δ-lactone-fused-CPs hotspots. This scaffold was also reactive enough to be incorporated into model cysteine-peptides in low concentrations, paving the way to a potential translation generating complexity in the synthesis of small peptides. The new enones also exhibited activity against intraerythrocytic Plasmodium falciparum (IC50 =1.32 µm).

Towards the sustainable discovery and development of new antibiotics.

An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.

Augmenting Adaptive Machine Learning with Kinetic Modeling for Reaction Optimization.

We combine random sampling and active machine learning (ML) to optimize the synthesis of isomacroin, executing only 3% of all possible Friedländer reactions. Employing kinetic modeling, we augment machine intuition by extracting mechanistic knowledge and verify that a global optimum was obtained with ML. Our study contributes evidence on the potential of multiscale approaches to expedite the access to chemical matter, further democratizing organic chemistry in a data-motivated fashion.