A regenerative approach for temporomandibular joint repair: An in vitro and ex vivo study.

BACKGROUND: Current clinical approaches to regenerate temporomandibular joint (TMJ) articulating cartilage defects only treat the symptoms (i.e. pain and dysfunction) and do not seek to restore joint integrity for long-term relief. Therefore, we investigated a novel self-assembling tissue-engineered cartilage to overcome this significant clinical issue for TMJ regenerative purposes. OBJECTIVES: Examine the maturation of dynamic self-regenerating cartilage (dSRC) using auricular chondrocytes and evaluate a novel combinatorial approach with fractional laser treatment and dSRC implantation for TMJ cartilage repair. MATERIALS AND METHODS: A suspension of 107 freshly harvested rabbit ear chondrocytes was cultured under a continuous reciprocating motion to form the dSRC. After 2, 4 and 8 weeks of culture, dSRC samples were stained with H&E, Safranin-O and Toluidine Blue. Immunohistochemistry (IHC) was performed for collagens type I and II. Channels (300-500 µm diameter and 1.2-1.5 mm depth) were created in six freshly harvested condyles using a fractional Erbium laser. Two groups were tested: dSRC in a laser-ablated lesion (experimental) and an empty laser-ablated channel (control). TMJ condyles were cultured for up to 8 weeks and analysed as described above. RESULTS: H&E staining showed a high cell density in dSRC compared to native cartilage. All dSRC groups demonstrated intense Safranin-O staining, indicating high glycosaminoglycan (GAG) production and intense Toluidine Blue staining showed high proteoglycan content. IHC confirmed that dSRC consisted predominantly of collagen type II. The experimental group showed improved cartilage repair at both time points compared to the empty channels. CONCLUSION: dSRC viability and successful matrix formation were demonstrated in vitro. The combination of fractional laser ablation and dSRC implantation enhanced cartilage repair.

Coding, Decoding and Retrieving a Message Using DNA: An Experience from a Brazilian Center Research on DNA Data Storage.

DNA data storage based on synthetic oligonucleotides is a major attraction due to the possibility of storage over long periods. Nowadays, the quantity of data generated has been growing exponentially, and the storage capacity needs to keep pace with the growth caused by new technologies and globalization. Since DNA can hold a large amount of information with a high density and remains stable for hundreds of years, this technology offers a solution for current long-term data centers by reducing energy consumption and physical storage space. Currently, research institutes, technology companies, and universities are making significant efforts to meet the growing need for data storage. DNA data storage is a promising field, especially with the advancement of sequencing techniques and equipment, which now make it possible to read genomes (i.e., to retrieve the information) and process this data easily. To overcome the challenges associated with developing new technologies for DNA data storage, a message encoding and decoding exercise was conducted at a Brazilian research center. The exercise performed consisted of synthesizing oligonucleotides by the phosphoramidite route. An encoded message, using a coding scheme that adheres to DNA sequence constraints, was synthesized. After synthesis, the oligonucleotide was sequenced and decoded, and the information was fully recovered.

Statine-based peptidomimetic compounds as inhibitors for SARS-CoV-2 main protease (SARS-CoV­2 Mpro).

COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50 < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.

Horizontal transfer and the widespread presence of Galileo transposons in Drosophilidae (Insecta: Diptera).

Galileo is a transposon notoriously involved with inversions in Drosophila buzzatii by ectopic recombination. Although widespread in Drosophila, little is known about this transposon in other lineages of Drosophilidae. Here, the abundance of the canonical Galileo and its evolutionary history in Drosophilidae genomes was estimated and reconstructed across genera within its two subfamilies. Sequences of this transposon were masked in these genomes and their transposase sequences were recovered using BLASTn. Phylogenetic analyses were employed to reconstruct their evolutionary history and compare it to that of host genomes. Galileo was found in nearly all 163 species, however, only 37 harbored nearly complete transposase sequences. In the remaining, Galileo was found highly fragmented. Copies from related species were clustered, however horizontal transfer events were detected between the melanogaster and montium groups of Drosophila, and between the latter and the Lordiphosa genus. The similarity of sequences found in the virilis and willistoni groups of Drosophila was found to be a consequence of lineage sorting. Therefore, the evolution of Galileo is primarily marked by vertical transmission and long-term inactivation, mainly through the deletion of open reading frames. The latter has the potential to lead copies of this transposon to become miniature inverted-repeat transposable elements.

Systematics and spatio-temporal evolutionary patterns of the flavopilosa group of Drosophila (Diptera, Drosophilidae).

The Drosophila flavopilosa group comprises morphologically cryptic species that are ecologically restricted to feeding, breeding and ovipositing on flowers of Cestrum and Sessea (Solanaceae). Previous studies confirmed the monophyly of the group and the success of DNA barcoding in identifying a subset of its species, but several others remain yet to be evaluated. Furthemore, the taxonomy of the group remains incomplete, with only nine of the 17 species assigned to subgroups. Here, we accessed the phylogenetic relationships and spatio-temporal evolutionary patterns of the flavopilosa group based on a mitochondrial and two nuclear genes, providing the first molecular support to the subdivision of the group and suggesting a new taxonomic scheme for its species. Barcoding proved to be an effective tool, as all species were reciprocally monophyletic and different analyses of species delimitation yielded congruent results. The close relationship of D. flavopilosa with D. cestri and D. cordeiroi was strongly supported, suggesting that the latter should be placed in the flavopilosa subgroup together with the first. Furthermore, D. mariaehelenae was positioned as sister to D. incompta, supporting its inclusion in the nesiota subgroup. Despite new taxonomic assignments, the synapomorphic status of the diagnostic characters proposed for both subgroups was supported. Based on them, each of the remaining species were placed into one of both subgroups. Divergence time estimates suggest that their diversification coincided with the divergence of Sessea and Cestrum, providing an interesting case of coevolution.

Rodents as an animal model for studying tooth extraction-related medication-related osteonecrosis of the jaw: assessment of outcomes.

OBJECTIVE: To assess the outcomes of several rodent animal models for studying tooth extraction-related medication-related osteonecrosis of the jaw (MRONJ). DESIGN: After a search of the databases, 2004 articles were located, and 118 corroborated the inclusion factors (in vivo studies in rodents evaluating tooth extraction as a risk factor for the development of MRONJ). RESULTS: Numerous studies attempting to establish an optimal protocol to induce MRONJ were found. Zoledronic acid (ZA) was the most used drug, followed by alendronate (ALN). Even when ZA did not lead to the development of MRONJ, its effect compromised the homeostasis of the bone and soft tissue. The association of other risk factors (dexamethasone, diabetes, and tooth-related inflammatory dental disease) besides tooth extraction also played a role in the development of MRONJ. In addition, studies demonstrated a relationship between cumulative dose and MRONJ. CONCLUSIONS: Both ZA and ALN can lead to MRONJ in rodents when equivalent human doses (in osteoporosis or cancer treatment) are used. Local oral risk factors and tooth-related inflammatory dental disease increase the incidence of MRONJ in a tooth extraction-related rodent model.

Growth Hormone Action in Somatostatin Neurons Regulates Anxiety and Fear Memory.

Dysfunctions in growth hormone (GH) secretion increase the prevalence of anxiety and other neuropsychiatric diseases. GH receptor (GHR) signaling in the amygdala has been associated with fear memory, a key feature of posttraumatic stress disorder. However, it is currently unknown which neuronal population is targeted by GH action to influence the development of neuropsychiatric diseases. Here, we showed that approximately 60% of somatostatin (SST)-expressing neurons in the extended amygdala are directly responsive to GH. GHR ablation in SST-expressing cells (SSTΔGHR mice) caused no alterations in energy or glucose metabolism. Notably, SSTΔGHR male mice exhibited increased anxiety-like behavior in the light-dark box and elevated plus maze tests, whereas SSTΔGHR females showed no changes in anxiety. Using auditory Pavlovian fear conditioning, both male and female SSTΔGHR mice exhibited a significant reduction in fear memory. Conversely, GHR ablation in SST neurons did not affect memory in the novel object recognition test. Gene expression was analyzed in a micro punch comprising the central nucleus of the amygdala (CEA) and basolateral (BLA) complex. GHR ablation in SST neurons caused sex-dependent changes in the expression of factors involved in synaptic plasticity and function. In conclusion, GHR expression in SST neurons is necessary to regulate anxiety in males, but not female mice. GHR ablation in SST neurons also decreases fear memory and affects gene expression in the amygdala, although marked sex differences were observed. Our findings identified for the first time a neurochemically-defined neuronal population responsible for mediating the effects of GH on behavioral aspects associated with neuropsychiatric diseases.SIGNIFICANCE STATEMENT Hormone action in the brain regulates different neurological aspects, affecting the predisposition to neuropsychiatric disorders, like depression, anxiety, and posttraumatic stress disorder. Growth hormone (GH) receptor is widely expressed in the brain, but the exact function of neuronal GH action is not fully understood. Here, we showed that mice lacking the GH receptor in a group of neurons that express the neuropeptide somatostatin exhibit increased anxiety. However, this effect is only observed in male mice. In contrast, the absence of the GH receptor in somatostatin-expressing neurons decreases fear memory, a key feature of posttraumatic stress disorder, in males and females. Thus, our study identified a specific group of neurons in which GH acts to affect the predisposition to neuropsychiatric diseases.

Maximal respiratory pressures: Measurements at functional residual capacity in individuals with different health conditions using a digital manometer.

BACKGROUND: Measuring maximal respiratory pressure is a widely used method of investigating the strength of inspiratory and expiratory muscles. OBJECTIVES: To compare inspiratory pressures obtained at functional residual capacity (FRC) with measures at residual volume (RV), and expiratory pressures obtained at FRC with measures at total lung capacity (TLC) in individuals with different health conditions: post-COVID-19, COPD, idiopathic pulmonary fibrosis (IPF), heart failure (CHF), and stroke; and to compare the mean differences between measurements at FRC and RV/TLC among the groups. METHODS: Inspiratory and expiratory pressures were obtained randomly at different lung volumes. Mixed factorial analysis of covariance with repeated measures was used to compare measurements at different lung volumes within and among groups. RESULTS: Seventy-five individuals were included in the final analyses (15 individuals with each health condition). Maximal inspiratory pressures at FRC were lower than RV [mean difference (95% CI): 11.3 (5.8, 16.8); 8.4 (2.3, 14.5); 11.1 (5.5, 16.7); 12.8 (7.1, 18.4); 8.0 (2.6, 13.4) for COVID-19, COPD, IPF, CHF, and stroke, respectively] and maximal expiratory pressures at FRC were lower than TLC [mean difference (95% CI): 51.9 (37.4, 55.5); 60.9 (44.2, 77.7); 62.9 (48.1, 77.8); 58.0 (43.9, 73.8); 57.2 (42.9, 71.6) for COVID-19, COPD, IPF, CHF, and stroke, respectively]. All mean differences were similar among groups. CONCLUSION: Although inspiratory and expiratory pressures at FRC were lower than measures obtained at RV/TLC for the five groups of health conditions, the mean differences between measurements at different lung volumes were similar among groups, which raises the discussion about the influence of the viscoelastic properties of the lungs on maximal respiratory pressure.

Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden.

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task was performed 30 and 120 days after the surgery, and sepsis accelerated the cognitive decline in APP/PS1 mice at both time points. At 120 days, the insoluble Aß increased in the sepsis group, and sepsis modulated the cytokines/chemokines, decreasing the cytokines associated with brain homeostasis IL-10 and IL-13 and increasing the eotaxin known to influence cognitive function. At 120 days, we found an increased density of IBA-1-positive microglia in the vicinity of Aß dense-core plaques, compared with the control group confirming the predictable clustering of reactive glia around dense-core plaques within 15 µm near Aß deposits in the brain. In the gut, sepsis negatively modulated the α- and ß-diversity indices evaluated by 16S rRNA sequencing, decreased the levels of SCFAs, and significantly affected ileum and colon morphology in CLP mice. Our data suggest that sepsis-induced peripheral infection accelerates cognitive decline and AD pathology in the AD mouse model.

Hypothalamic Kisspeptin Neurons as a Target for Whole-Cell Patch-Clamp Recordings.

Kisspeptins are essential for the maturation of the hypothalamic-pituitary-gonadal (HPG) axis and fertility. Hypothalamic kisspeptin neurons located in the anteroventral periventricular nucleus and rostral periventricular nucleus, as well as the arcuate nucleus of the hypothalamus, project to gonadotrophin-releasing hormone (GnRH) neurons, among other cells. Previous studies have demonstrated that kisspeptin signaling occurs through the Kiss1 receptor (Kiss1r), ultimately exciting GnRH neuron activity. In humans and experimental animal models, kisspeptins are sufficient for inducing GnRH secretion and, consequently, luteinizing hormone (LH) and follicle stimulant hormone (FSH) release. Since kisspeptins play an essential role in reproductive functions, researchers are working to assess how the intrinsic activity of hypothalamic kisspeptin neurons contributes to reproduction-related actions and identify the primary neurotransmitters/neuromodulators capable of changing these properties. The whole-cell patch-clamp technique has become a valuable tool for investigating kisspeptin neuron activity in rodent cells. This experimental technique allows researchers to record and measure spontaneous excitatory and inhibitory ionic currents, resting membrane potential, action potential firing, and other electrophysiological properties of cell membranes. In the present study, crucial aspects of the whole-cell patch-clamp technique, known as electrophysiological measurements that define hypothalamic kisspeptin neurons, and a discussion of relevant issues about the technique, are reviewed.

Effects of periodontitis on cancer outcomes in the era of immunotherapy.

Periodontitis results from dysbiosis of the oral microbiome and affects up to 70% of US adults aged 65 years and older. More than 50 systemic inflammatory disorders and comorbidities are associated with periodontitis, many of which overlap with immunotherapy-associated toxicities. Despite the increasing use of immunotherapy for the treatment of cancer, uncertainty remains as to whether the microbial shift associated with periodontal disease can influence response rates and tolerance to cancer immunotherapy. We herein review the pathophysiology of periodontitis and the local and systemic inflammatory conditions related to oral dysbiosis, and discuss the overlapping adverse profiles of periodontitis and immunotherapy. The effects of the presence of Porphyromonas gingivalis, a key pathogen in periodontitis, highlight how the oral microbiome can affect the hosts' systemic immune responses, and further research into the local and systemic influence of other microorganisms causing periodontal disease is necessary. Addressing periodontitis in an ageing population of people with cancer could have potential implications for the clinical response to (and tolerability of) immunotherapy and warrants further investigation.

Patterns of genome size evolution versus fraction of repetitive elements in statu nascendi species: the case of the willistoni subgroup of Drosophila (Diptera, Drosophilidae).

Genome size evolution is known to be related with transposable elements, yet such relation in incipient species remains poorly understood. For decades, the willistoni subgroup of Drosophila has been a model for evolutionary studies because of the different evolutionary stages and degrees of reproductive isolation its species present. Our main question here was how speciation influences genome size evolution and the fraction of repetitive elements, with a focus on transposable elements. We quantitatively compared the mobilome of four species and two subspecies belonging to this subgroup with their genome size, and performed comparative phylogenetic analyses. Our results showed that genome size and the fraction of repetitive elements evolved according to the evolutionary history of these species, but the content of transposable elements showed some discrepancies. Signals of recent transposition events were detected for different superfamilies. Their low genomic GC content suggests that in these species transposable element mobilization might be facilitated by relaxed natural selection. Additionally, a possible role of the superfamily DNA/TcMar-Tigger in the expansion of these genomes was also detected. We hypothesize that the undergoing process of speciation could be promoting the observed increase in the fraction of repetitive elements and, consequently, genome size.

Neurochemical effects of sepsis on the brain.

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB function. The resulting BBB permeability allows peripheral immune cells from the bloodstream to enter the brain, which then release a range of inflammatory mediators and activate glial cells. The activated microglia and astrocytes release reactive oxygen species (ROS), cytokines, chemokines, and neurochemicals, initiate mitochondrial dysfunction and neuronal damage, and exacerbate the inflammatory milieu in the brain. These changes trigger sepsis-associated encephalopathy (SAE), which has the potential to increase cognitive deterioration and susceptibility to cognitive decline later in life.

New, fast, and precise method of COVID-19 detection in nasopharyngeal and tracheal aspirate samples combining optical spectroscopy and machine learning.

Fast, precise, and low-cost diagnostic testing to identify persons infected with SARS-CoV-2 virus is pivotal to control the global pandemic of COVID-19 that began in late 2019. The gold standard method of diagnostic recommended is the RT-qPCR test. However, this method is not universally available, and is time-consuming and requires specialized personnel, as well as sophisticated laboratories. Currently, machine learning is a useful predictive tool for biomedical applications, being able to classify data from diverse nature. Relying on the artificial intelligence learning process, spectroscopic data from nasopharyngeal swab and tracheal aspirate samples can be used to leverage characteristic patterns and nuances in healthy and infected body fluids, which allows to identify infection regardless of symptoms or any other clinical or laboratorial tests. Hence, when new measurements are performed on samples of unknown status and the corresponding data is submitted to such an algorithm, it will be possible to predict whether the source individual is infected or not. This work presents a new methodology for rapid and precise label-free diagnosing of SARS-CoV-2 infection in clinical samples, which combines spectroscopic data acquisition and analysis via artificial intelligence algorithms. Our results show an accuracy of 85% for detection of SARS-CoV-2 in nasopharyngeal swab samples collected from asymptomatic patients or with mild symptoms, as well as an accuracy of 97% in tracheal aspirate samples collected from critically ill COVID-19 patients under mechanical ventilation. Moreover, the acquisition and processing of the information is fast, simple, and cheaper than traditional approaches, suggesting this methodology as a promising tool for biomedical diagnosis vis-à-vis the emerging and re-emerging viral SARS-CoV-2 variant threats in the future.

Impact of pivoting bite tip on bite force measurement tests.

OBJECTIVE: Present a gnathodynamometer design that increases patient comfort, precision, and/or ease for the operator during bite force tests. MATERIALS AND METHODS: A bite tip capable of pivoting 180° was tested on senior dental students in a double-blind trial. The tests were performed in teeth 11 and 16 with the bite tip on the long axis of the clamp and at an angle of 90° to the clamp. The sample was composed of 24 students, 13 males and 11 females, randomly divided into two groups: the operator group (OP), which was composed of 12 students, 7 males and 5 females, and the test group (TI), which was composed of 12 students, 6 males and 6 females. The operator and participants were asked to evaluate comfort and precision/ease in positioning the bite tip by attributing scores from 0 (total discomfort) to 10 (total comfort) during the test. RESULTS: No difference was noted in tooth 11 (P > 0.05). In tooth 16, there was a statistically significant improvement (P < 0.01) for the participants tested and the operator using the pivoting bite tip. CONCLUSIONS: The pivoting bite tip showed no difference in the comfort of the participants and operator precision when testing incisors; however, the tip showed a difference for both conditions in the molar region. The gnathodynamometer geometry showed good results in participant comfort and operator precision when used in bite force tests of the incisors and molars. Further investigations are needed to confirm whether these improvements influence the mean value and maximum bite force measurement. CLINICAL RELEVANCE: Bite force measurement is a method for obtaining important data to check the functional conditions of the stomatognathic system. With the aging of the world population, it has become important to check the quality of life during aging. The pivoting bite tip improves the comfort and precision of bite tests for the participants tested and for the operator, respectively.

Photo-crosslinked GelMA loaded with dental pulp stem cells and VEGF to repair critical-sized soft tissue defects in rats.

BACKGROUND: Tissue engineering of skin and mucosa is essential for the esthetic and functional reconstruction of individuals disfigured by trauma, resection surgery, or severe burns while overcoming the limited amount of autograft and donor site morbidity. PURPOSE: We aimed to determine whether a combination of Gelatin-methacryloyl (GelMA) hydrogel scaffold alone or loaded with either dental pulp stem cells (DPSCs) and/or vascular endothelial growth factor (VEGF) could improve skin wound healing in rats. MATERIALS AND METHODS: Four 10 mm full-thickness skin defects were created on the dorsum of 15 Sprague-Dawley rats. The wounds were treated with GelMA alone, GelMA+DPSCs, or GelMA+DPSCs+VEGF. Unprotected wounds were used as controls. Animals were euthanized at 1-, 2-, and 4 weeks post-surgery, and the healing wounds were harvested for clinical, histological, and RT-PCR analysis. RESULTS: No signs of clinical inflammation were observed among all groups. Few and sparse mononuclear inflammatory cells were observed in GelMA+DPSCs and GelMA+DPSCs+VEGF groups at 2 weeks, with complete epithelialization of the wounds. At 4 weeks, the epidermis in GelMA+DPSCs and GelMA+DPSCs+VEGF groups was indistinguishable from the empty defect and GelMA groups. The decrease in cellularity and increase in density of collagen fibers were observed over time in both GelMA+DPSCs and GelMA+DPSCs+VEGF groups but were more evident in the GelMA+DPSCs+VEGF group. The GelMA+DPSCs+VEGF group showed a higher expression of the KER 10 gene at all time points compared with the other groups. Expression of Col1 A1 and TGFß-1 were not statistically different over time neither among the groups. CONCLUSION: GelMA scaffolds loaded with DPSCs, and VEGF accelerated the re-epithelialization of skin wounds.

Molecular Modeling, Virtual Screening, and Molecular Dynamics for Leishmania infantum Methionyl-tRNA Synthetase.

Visceral leishmaniasis is a neglected tropical disease (NTD) caused by Leishmania infantum and L. donovani that is lethal in cases of nontreatment. The treatments are limited by serious drawbacks involving safety, resistance, stability, and high costs. In this work, we aimed to identify inhibitors of Leishmania infantum methionyl-tRNA synthetase (LiMetRS), a validated molecular target for leishmaniasis drug discovery, using a combination of strategies. A virtual database of compounds was organized by filtering compounds from the ZINC15 database. Homology modeling was used to obtain the structure of LiMetRS based on the crystal coordinates of the enzyme from Trypanosoma brucei (TbMetRS). A virtual screening using molecular docking identified 10 candidate compounds from among more than 5 million that were included in the initial database. The selected hits were further evaluated using a script created in this work to select only the ligands that interacted with specific amino acids in the catalytic site of the enzyme. Furthermore, suitable pharmacokinetic profiles were predicted for the selected compounds, especially a good balance between aqueous solubility and lipophilic character, no ability to cross the blood-brain barrier, good oral absorption, and no liability toward P-gp efflux for most compounds. Six compounds were then subjected to all-atom molecular dynamics. Two compounds showed good stability when bound to the leishmanial enzyme, which provided a deeper understanding of the structural differences between TbMetRS and LiMetRS that can guide further drug discovery efforts for visceral leishmaniasis.

Post-legalization Consumption of Cannabis at Massachusetts General Hospital Dental Group.

AIM: The aim of this study was to evaluate the profile of patients undergoing dental treatment in relation to cannabis use. MATERIALS AND METHODS: A comprehensive questionnaire was used to address the type of cannabis preparations, route of intake, frequency of usage, and potential reasoning for use (recreational vs medical use) of patients from the MGH Dental Group. RESULTS: Seventy-six adult patients completed the survey. Sixty-one percent of the participants were female, with the majority (59%) of the participants being ≥51 years or older. Twelve of the 76 participants (16%) were 18-30 years old. The remaining 19 patients (25%) who participated in the study were 31-50 years old. The sample included participants who were predominately non-Hispanic (63 patients, 83%) and White (59 patients, 78%). The majority of patients either had their first use of cannabis prior to 18 years of age (36%) or did not respond to this question (34%) at all. The predominant age at consistent cannabis use was 18-30 years (13%). The most common method of cannabis intake in the preceding year for participants was smoking, followed by ingesting, using cannabidiol (CBD), and vaping (least common). Recreational cannabis use was reported in 47% of the participants vs 28% of participants who reported cannabis intake for medical use. CONCLUSION: This preliminary study characterized the profile of patients undergoing dental treatment in relation to marijuana use. Diminishing restraints to cannabis use may affect the dental profession. CLINICAL SIGNIFICANCE: It is important for dentists to understand cannabis-related oral health conditions to provide customized patient treatments.