Analysis of the stomatognathic system functions and mastication muscles in children affected by molar hypomineralization (MH): a cross-sectional study.

PURPOSE: To analyze the functions of the stomatognathic system in children with or without molar-incisor hypomineralization (MIH). METHODS: For this cross-sectional study, 72 children aged 6-12 years were recruited and divided in two groups: with MIH (G1) and without MIH (G2). T-SCAN was used to verify the distribution of occlusal contacts, gnathodynamometer to measure maximum molar bite force, and Iowa Oral Pressure Instrument (IOPI) to assess the strength of facial expression muscles. The t test and paired t test (p ≤ 0.05) were used for statistical comparisons. RESULTS: The molars affected by MIH exhibited lower distribution of occlusal forces (p < 0.001) and lower maximum molar bite force (p < 0.05) compared to the molars in the control group. However, there was no difference between the MIH-affected sides compared to the unaffected side, nor between the molars affected by MIH and their antagonists (p > 0.05). There were no differences in the forces of the facial expression muscles between the groups. CONCLUSIONS: These findings suggest that MIH significantly impacts occlusal force distribution and bite force, but not facial expression musculature.

2-Aryladenine Derivatives as a Potent Scaffold for Adenosine Receptor Antagonists: The 6-Morpholino Derivatives.

A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A1, A2A, A2B, and A3 adenosine receptor subtypes. Eleven purines showed potent antagonism at A1, A3, dual A1/A2A, A1/A2B, or A1/A3 adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs.

DNA mismatch repair system expression in salivary gland tumors: A Systematic Review.

BACKGROUND: The DNA mismatch repair (MMR) system serves as a sophisticated guardian of the precise functioning of the human genome. Dysregulation within this system is linked to the oncogenesis process. Reduced expression of MMR system proteins identified in salivary gland tumors (SGTs) suggests an increased risk of tumoral occurrence. This study aims to analyze the expression of MMR proteins in SGTs and discuss the relevance of this association to the development of these neoplasms. MATERIAL AND METHODS: This review was conducted following the PRISMA guidelines and was registered in PROSPERO (CRD42023465590). A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, Embase, and ProQuest (non-peer reviewed platform) was performed to answer the question "Do DNA MMR system proteins exhibit expression in SGTs?". The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool. RESULTS: A total of 142 patients with benign SGTs and 84 with malignant SGTs were included in this review. The literature analysis showed a notable reduction in the expression of DNA MMR system proteins (hHMS2, hMLH1, hMSH3 and hMSH6) in the percentage of marked cells. CONCLUSIONS: The reduction in the expression of the DNA MMR system proteins suggests an interesting correlation with the development of malignant and benign SGTs. Nevertheless, further investigations are warranted to better clarify the precision of measuring biomarker protein expression.

Discovery of 2,9-diaryl-6-carbamoylpurines as a novel class of antitubercular agents.

A series of novel 9-alkyl/aryl-2-aryl-6-carbamoylpurines were synthesized, and their activity against Mycobacterium tuberculosis strain H37Rv was assessed. The SAR analysis on the first set of derivatives, with an alkyl or aryl unit at N-9 and a phenolic unit at C-2, showed that the activity depends on the purine ring substituents at N-9 and C-2. A phenyl group at N-9 combined with a 3-hydroxyphenyl or 4-hydroxyphenyl at C-2 improve the activity. The most active compound of this set has a phenyl group at N-9 and a 4-hydroxyphenyl group at C-2, displaying an IC90 = 1.2 µg/mL and a selectivity index higher than 25.5. This compound served as a Hit to design the second set of derivatives. A phenyl group at N-9 was maintained, and the group at C-2 was diversified. The SAR analysis showed that the aryl unit at C-2 must have an oxygen or nitrogen atom bonded in the para position. A proton, a small alkyl or a substituted aryl group may also be bonded to the oxygen. The compound with the 4-methoxyphenyl group at C-2, 1Bd, exhibits the highest activity with an IC90 < 0.19 µg/mL. This compound is highly potent against M. tuberculosis strain H37Rv and non-toxic for VERO mammalian cells with an SI > 153.8. Compound 1Bd was also non-cytotoxic against primary macrophage cultures at IC90, 2xIC90, and 10xIC90 and significantly reduced the bacterial load in M. tuberculosis-infected macrophages at the same concentrations. Compound 1Bd showed a favorable pharmacokinetic profile when administered orally, with major lung and liver accumulation. In vivo antimycobacterial efficacy of 1Bd was tested at 25 mg/kg. At the tested regimen, a decrease in bacterial burden was observed in the liver. Optimization of the treatment regimen should be performed to fully potentiate the in vivo efficacy of our lead molecule, particularly in the lung, the main target organ of M. tuberculosis.

Characterisation of colistin resistance in Gram-negative microbiota of pregnant women and neonates in Nigeria.

A mobile colistin resistance gene mcr was first reported in 2016 in China and has since been found with increasing prevalence across South-East Asia. Here we survey the presence of mcr genes in 4907 rectal swabs from mothers and neonates from three hospital sites across Nigeria; a country with limited availability or history of colistin use clinically. Forty mother and seven neonatal swabs carried mcr genes in a range of bacterial species: 46 Enterobacter spp. and single isolates of; Shigella, E. coli and Klebsiella quasipneumoniae. Ninety percent of the genes were mcr-10 (n = 45) we also found mcr-1 (n = 3) and mcr-9 (n = 1). While the prevalence during this collection (2015-2016) was low, the widespread diversity of mcr-gene type and range of bacterial species in this sentinel population sampling is concerning. It suggests that agricultural colistin use was likely encouraging sustainment of mcr-positive isolates in the community and implementation of medical colistin use will rapidly select and expand resistant isolates.

Xylanase treatment of eucalypt kraft pulps: effect of carryover.

The influence of pulp carryover on the efficiency of the xylanase (X) treatment of industrial unbleached and oxygen-delignified eucalypt kraft pulps (A1 and A2 pulps, with kappa number (KN) values of 16 and 10, respectively), collected at the same pulp mill, was studied regarding the consumption of bleaching chemicals and pulp bleachability. Another non-oxygen-delignified eucalyptus kraft pulp of KN 13 was received after the extended cooking from a different pulp mill (pulp B). The assays were performed with both lab-washed (carryover-free) and unwashed (carryover-rich) pulps. Both lab-washed and unwashed pulps with carryover were subjected to X treatment, the former being demonstrating considerably higher ClO2 savings than the pulps containing carryover. The savings of bleaching reagents were higher when the X stage was applied to the A1 pulp than to the A2 pulp. This advantage of A1 pulp, however, was not confirmed when using unwashed pulps. In contrast, the gains obtained from the X treatment of unwashed pulp A2 were practically as high as those observed for the lab-washed A2 pulp. Furthermore, a similar effect in X stage was recorded for unwashed pulps having close KN: oxygen-delignified A2 pulp and non-oxygen-delignified B pulp. The results suggest that pulp carryover and initial pH were the key factors relating to the effectiveness of X treatment. The application of X treatment to the A2 unwashed pulp (after the oxygen stage) not only saved 20% of the ClO2 and 10% of the sodium hydroxide, but also improved the brightness stability of the bleached pulp without affecting its papermaking properties. KEY POINTS: • Xylanase treatment boosts kraft pulp bleaching • Pulp carryover hinders the xylanase treatment • Nearly 20% of ClO2 and 10% NaOH savings can be reached using xylanase.

Characterization of time-dependence for dissipative solitons stabilized by nonlinear gradient terms: Periodic and quasiperiodic vs chaotic behavior.

We investigate the properties of time-dependent dissipative solitons for a cubic complex Ginzburg-Landau equation stabilized by nonlinear gradient terms. The separation of initially nearby trajectories in the asymptotic limit is predominantly used to distinguish qualitatively between time-periodic behavior and chaotic localized states. These results are further corroborated by Fourier transforms and time series. Quasiperiodic behavior is obtained as well, but typically over a fairly narrow range of parameter values. For illustration, two examples of nonlinear gradient terms are examined: the Raman term and combinations of the Raman term with dispersion of the nonlinear gain. For small quintic perturbations, it turns out that the chaotic localized states are showing a transition to periodic states, stationary states, or collapse already for a small magnitude of the quintic perturbations. This result indicates that the basin of attraction for chaotic localized states is rather shallow.

Maturation and harvest time of Ateleia glazioveana Baill. seeds.

Ateleia glazioveana Baill. is a pioneer, rustic and can be used for forest recovery. This work aimed to study the process of physiological maturation of this species. The research was carried out in the city of Alegre - ES, the trees were identified in the floral anthesis and accompanied during the filling of the fruits and development of the seeds until the complete maturation. The fruits were harvested at the following stages 7, 14, 21, 28, 35 and 42 days after anthesis, and characterized according to: morphometry, moisture, fresh and dry mass of fruits and seeds, germination, germination speed index, shoot and root length and dry mass of seedlings. The regression equations were adjusted for the main characteristics analyzed as a function of the harvest period. The point of physiological maturity of timbó occurred at 42 days after anthesis.

Quartic solitons of a mode-locked laser distributed model.

Dissipative quartic solitons have gained interest in the field of mode-locked lasers for their energy-width scaling which allows the generation of ultrashort pulses with high energies. Pursuing the characterization of such pulses, here we found soliton solutions of a distributed model for mode-locked lasers in the presence of either positive or negative fourth-order dispersion (4OD). We studied the impact the laser parameters may have on the profiles, range of existence, and energy-width relation of the output pulses. The most energetic and narrowest solutions occur for negative 4OD, with the energy having an inverse cubic dependence with the width in most cases. Our simulations showed that the spectral filtering has the biggest contribution in the generation of short (widths as low as 39 fs) and very energetic (391 nJ) optical pulses.

Evolution of the triplet BRCT domain.

Organisms have evolved a complex system, called the DNA damage response (DDR), which maintains genome integrity. The DDR is responsible for identifying and repairing a variety of lesions and alterations in DNA. DDR proteins coordinate DNA damage detection, cell cycle arrest, and repair, with many of these events regulated by protein phosphorylation. In the human proteome, 23 proteins contain the BRCT (BRCA1 C-Terminus domain) domain, a modular signaling domain that can bind phosphopeptides and mediate protein-protein interactions. BRCTs can be found as functional single units, tandem (tBRCT), triplet (tpBRCT), and quartet. Here we examine the evolution of the tpBRCT architecture present in TOPBP1 (DNA topoisomerase II binding protein 1) and ECT2 (epithelial cell transforming 2), and their respective interaction partners RAD9 (Cell cycle checkpoint control protein RAD9) and CYK-4 (Rac GTPase-activating protein 1), with a focus on the conservation of the phosphopeptide-binding residues. The pair TOPBP1-RAD9 arose with the Eukaryotes and ECT2-CYK-4 with the Eumetazoans. Triplet structural and functional characteristics were conserved in almost all organisms. The first unit of the triplet (BRCT0) is different from the other two BRCTs but conserved between orthologs for both TOPBP1 and ECT2. BRCT domain evolution simulations suggest a trend to retain the singlet or towards two or three BRCT copies per protein consistent with functional tBRCT and tpBRCT architectures. Our results shed light on the emergence of the function and architecture of multiple BRCT domain organizations and provide information about the evolution of the BRCT triplet. Knowledge of BRCT domain evolution can improve the understanding of DNA damage response mechanisms and signal transduction in DDR.

Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres.

OBJECTIVE: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS: Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Association of dental hypersensitivity and anxiety in children with molar-incisor hypomineralisation (MIH).

AIM: The objective of this study was to investigate whether dental hypersensitivity and dental fear were linked to the presence and severity of MIH. METHODS: For this cross-sectional study, 1830 students between the ages of 6 and 12 years were recruited from four randomly selected schools. The Children's Fear Survey Schedule-Dental Subscale questionnaire was used to assess dental anxiety and fear. The children's self-reported dental hypersensitivity resulting from MIH was evaluated using the Wong-Baker Facial Scale and the Visual Analog Scale (VAS). RESULTS: MIH was correlated with tooth hypersensitivity, particularly in severe cases. Dental fear was present in 17.4% of the children with MIH, but it was not associated with dental hypersensitivity, gender, or age. CONCLUSION: No association was found between dental fear and dental hypersensitivity in children with MIH.

A Series of Non-Oxido VIV Complexes of Dibasic ONS Donor Ligands: Solution Stability, Chemical Transformations, Protein Interactions, and Antiproliferative Activity.

A series of mononuclear non-oxido vanadium(IV) complexes, [VIV(L1-4)2] (1-4), featuring tridentate bi-negative ONS chelating S-alkyl/aryl-substituted dithiocarbazate ligands H2L1-4, are reported. All the synthesized non-oxido VIV compounds are characterized by elemental analysis, spectroscopy (IR, UV-vis, and EPR), ESI-MS, as well as electrochemical techniques (cyclic voltammetry). Single-crystal X-ray diffraction studies of 1-3 reveal that the mononuclear non-oxido VIV complexes show distorted octahedral (1 and 2) or trigonal prismatic (3) arrangement around the non-oxido VIV center. EPR and DFT data indicate the coexistence of mer and fac isomers in solution, and ESI-MS results suggest a partial oxidation of [VIV(L1-4)2] to [VV(L1-4)2]+ and [VVO2(L1-4)]-; therefore, all these three complexes are plausible active species. Complexes 1-4 interact with bovine serum albumin (BSA) with a moderate binding affinity, and docking calculations reveal non-covalent interactions with different regions of BSA, particularly with Tyr, Lys, Arg, and Thr residues. In vitro cytotoxic activity of all complexes is assayed against the HT-29 (colon cancer) and HeLa (cervical cancer) cells and compared with the NIH-3T3 (mouse embryonic fibroblast) normal cell line by MTT assay and DAPI staining. The results suggest that complexes 1-4 are cytotoxic in nature and induce cell death in the cancer cell lines by apoptosis and that a mixture of VIV, VV, and VVO2 species could be responsible for the biological activity.

AM-879, a PPARy non-agonist and Ser273 phosphorylation blocker, promotes insulin sensitivity without adverse effects in mice.

Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists.

Wasted leg syndrome: An atypical slowly-progressive form of lower motor neuron disease.

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7-18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patient was later diagnosed with CADASIL. Electromyography (EMG) revealed severe chronic neurogenic changes in proximal leg muscles, and mild changes in distal leg muscles, but EMG of the upper limbs was normal. Upper motor neuron signs were absent clinically and on transcranial magnetic stimulation. This seems to represent a variant of the common wasted-leg syndrome presentation.

N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes.

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 µg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

Chemical data of contaminants in water and sediments from the Doce River four years after the mining dam collapse disaster.

Chemical datasets describing the occurrence of both inorganic and organic contaminants along the Doce River Basin (DRB) could provide a better understanding of the potential impacts of a major mining dam collapse disaster combined to additional chronic sources of contamination. This data article presents datasets of main contaminants detected in the water and sediments sampled four years after the mining dam collapse in the DRB. A summary table of data obtained in the literature is also provided to allow a comparison of the variation of chemicals before, right after in 2015/2016 and after the event (current data). In addition, there are also provided physical-chemical parameters of water and sediments of different sampling sites, which could support the investigation of chemicals distribution. For this purpose, triplicate samples of water and sediment were obtained in 8 sampling sites along the DRB during wet and dry seasons of 2019, totalizing 48 samples of each environmental matrix. The sampling sites were strategically selected according to their different main sources of pollution along the river. Concentrations of trace elements and organic contaminants (polycyclic aromatic hydrocarbons, and pyrethroids) were determined in samples of water and sediments by inductively coupled plasma mass spectrometry (ICP-MS) and gas chromatography - mass spectrometry GC-MS, respectively. Main data obtained in the literature consisted in published reports from environmental agencies (IGAM) and private companies (RENOVA) as well as journal articles. The datasets provided may be useful to the stakeholders, which include scientific community, authorities and public agencies, and private companies interested to understand the impacts of the contaminants introduced along the River Basin four years after the environmental disaster.

Pyrimido[5,4-d]pyrimidine-Based Compounds as a Novel Class of Antitrypanosomal and Antileishmanial Agents.

Sleeping sickness and leishmaniasis are neglected tropical diseases that threaten millions of people. The currently available therapies present several limitations, including high toxicity, lack of efficacy, and emerging drug resistance, prompting a search for novel therapeutic agents. In this work, we designed, synthesized, and in vitro evaluated the activity of new pyrimido[5,4-d]pyrimidines against Trypanosoma brucei and Leishmania infantum (promastigote and amastigote forms). The cytotoxicity of the compounds against the THP1 cell line was also assessed. Most tested compounds presented low micromolar activity against T. brucei with IC50 values in the range between 0.9 and 13.4 µM, and one compound also showed activity against L. infantum (IC50 = 3.13 µM). Several molecules presented a selectivity index higher than 10. The most active compound against booth parasites is derivative 4c, with IC50 = 0.94 µM (SI > 107) against T. brucei and IC50 = 3.13 µM (SI > 32) against L. infantum. This data enabled the identification of a new promising molecular scaffold for developing a novel class of antitrypanosomal and antileishmanial agents.