Association between obstructive sleep apnea and temporomandibular disorders: A meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is a very common condition in patients with temporomandibular disorders (TMD). However, there is little evidence of a connection between them. OBJECTIVE: The aim of this systematic review and meta-analysis is to assess the association between OSA and TMD in adult population. METHODS: Case-control, cross-sectional and cohort studies on the association between TMD and OSA were searched in the EMBASE, LILACS, LIVIVO, PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, Open Grey and Pro Quest databases. TMD should be assessed using Research Diagnostic Criteria (RDC/TMD) or Diagnostic Criteria (DC/TMD) and OSA using polysomnography (PSG) and/or a validated questionnaire. The risk of bias was evaluated using the Joanna Briggs Institute Critical Assessment Checklists; and an association meta-analysis was performed. The effect measure included the odds ratio (OR) in dichotomous variables and a 95% confidence interval (CI). Certainty of evidence was determined by analysing groups using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Out of the 1024 articles screened, 7 met the inclusion criteria for the qualitative synthesis, and 6 for quantitative analysis. All articles were classified at low risk of bias. A positive association with OSA was found in patients with TMD (OR = 2.61; 95% CI = 2.31, 2.95). A significant association was also found irrespective to the OSA diagnostic methods applied (for studies using PSG + validated questionnaires: OR = 2.74; 95% CI = 2.11, 3.57; for studies using validated questionnaires only: OR = 2.55; 95% CI = 2.22, 2.92). GRADE was moderate. CONCLUSION: Patients with TMD presented a significant association with OSA regardless of the OSA diagnostic method (PSG and/or validated questionnaires). OSA screening should be part of the TMD examination routine. Furthermore, due to the different OSA assessment methods used and the small number of studies included, there is a need to include a larger number of studies using PSG to better elucidate this association.

Multispecies and multibiomarker assessment of fish health from Iguaçu River reservoir, Southern Brazil.

This study investigated the impact of micropollutants on fish health from Segredo hydroelectric reservoir (HRS) along the Iguaçu River, Southern Brazil, contaminated by urban, industrial, and agricultural activities. This is the first comprehensive study assessment in the river after the severe drought in the 2020s in three fish species from different trophic levels Astyanax spp. (water column depth/omnivorous), Hypostomus commersoni (demersal/herbivorous), and Pimelodus maculatus (demersal/omnivorous). Animals, water, and sediment samples were collected from three distinct sites within the reservoir: Floresta (upstream), Iratim (middle), and Station (downstream). The chemical analysis revealed elevated concentrations of metals (Al, Cu, Fe) and the metalloid As in water, or Cu, Zn, and As in sediment, surpassing Brazilian regulatory limits, while the organic pollutants as DDT, PAHs, PCBs, and PBDEs were found under the Brazilian regulatory limits. The metal bioaccumulation was higher in gills with no significant differences among sites. The species Astyanax spp. and H. commersoni displayed variations in hepatosomatic index (HSI) and P. maculatus in the condition factor index (K) between sites, while adverse effects due to micropollutants bioaccumulation were observed by biochemical, genotoxic, and histopathological biomarkers. The principal component analysis and integrated biomarker response highlighted the upstream site Floresta as particularly inhospitable for biota, with distinctions based on trophic level. Consequently, this multifaceted approach, encompassing both fish biomarkers and chemical analyses, furnishes valuable insights into the potential toxic repercussions of micropollutant exposure. These findings offer crucial data for guiding management and conservation endeavors in the Iguaçu River.

Application of workload indicators to assess the allocation of orthopedists in a national referral hospital in Brazil.

BACKGROUND: The study analyzes the allocation of specialized doctors' orthopedists in a high-complex hospital, using the WHO's Workload Indicators of Staffing Need (WISN) methodology and approach, which measures the workload pressure on the healthcare team (positive, negative, or well-adjusted). METHODS: In the first phase, the hospital's operations and activities were analyzed using the information system. The duration of the tasks performed by the specialist physicians was observed and directly measured in the second phase. Finally, the indicators were analyzed, and the workload was calculated using the WISN application. The measurement was made using the available work time per year divided by the time unit over the previous 12 months. RESULTS: The hand surgery care unit was WISN 1.0 and the ratios for the spine surgery care unit was 1.22, indicating enough physicians and no work overload among the groups surveyed. The ratio in the knee unit was 1.69, indicating that there was an excess of staffing for the workload. CONCLUSION: The workload findings and staffing calculations were useful in supporting and orienting the design and implementation of measures to increase the efficiency and effectiveness of health services.

Evaluation of testicular structure in mice after exposure to environmentally relevant doses of manganese during critical windows of development.

Despite being an essential trace element with great importance for vital metabolic activities, the manganese (Mn) can also cause damage to organ systems. However, data on the effect of this metal on the male reproductive system are limited, especially using relevant doses to human exposure. The present study aimed to evaluate and compare the effects of Mn exposure on the testicular structure of mice. Three experiments were conducted: (I) direct exposure to realistic doses (0.013, 0.13, and 1.3 mg/kg/day of MnCl2); (II) parental and direct exposure to realistic doses (as in experiment I), where the animals were exposed during intrauterine development and from lactation until reproductive maturity; (III) direct exposure to high doses (15, 30, and 60 mg/kg/day of MnCl2). Biometric, histopathological, histomorphometric and stereological parameters of the testis were evaluated, in addition to sperm morphology. Bioinformatic analyses were performed to identify potential Mn binding sites in 3ß-HSD and P450ssc, as well as their protein-protein interaction network. The results obtained were compared using the integrated biomarker response index (IBR). There was an increase of seminiferous tubules pathologies in all experimental conditions tested, with effects on tubular volume, as well as a reduction in tubular diameter. The IBR analyses showed that parental and direct exposure had a significant negative effect on the testicular structure due to the exposure of this metal to sensitive periods of animal development. This study suggests that Mn has the potential to alter the morphological parameters of the testes, affecting the spermatogenesis in mice.

Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs.

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments.

Inflammation is central in intervertebral disc (IVD) degeneration/regeneration mechanisms, and its balance is crucial to maintain tissue homeostasis. This work investigates the modulation of local and systemic inflammatory response associated with IVD degeneration/herniation by administration of PRO- versus ANTI-inflammatory treatments. Chitosan/poly-γ-glutamic acid nanocomplexes, known as pro-inflammatory (PRO), and soluble diclofenac, a non-steroidal anti-inflammatory drug (ANTI), were intradiscally administered in a rat IVD injury model, 24 h after lesion. Two weeks after administration, a reduction of disc height accompanied by hernia formation was observed. In the PRO-inflammatory treated group, IL-1ß, IL-6 and COX-2 IVD gene expression were upregulated, and loss of nucleus pulposus (NP) structure and composition was observed. Systemically, lower T-cell frequency was observed in the lymph nodes (LN) and spleen (SP) of the PRO group, together with an increase in CD4+ T cells subset in the blood (BL) and LN. In contrast, the ANTI-group had higher proteoglycans/collagen ratio and collagen type 2 content in the NP, while an increase in the frequency of myeloid cells, M1 macrophages and activated macrophages (MHCII+) was observed at the systemic level. Overall, this study illustrates the dynamics of local and systemic inflammatory and immune cell responses associated with intradiscal therapies, which will contribute to designing more successful immunomodulatory treatments for IVD degeneration.

Diffuse sources of contamination in freshwater fish: Detecting effects through active biomonitoring and multi-biomarker approaches.

Aquatic organisms are usually exposed to a mixture of xenobiotics that may exert a large effect even in low concentrations, and when information is obtained exclusively from chemical analyses the prediction of the deleterious effects is potentially hindered. Therefore, the application of complementary monitoring methods is a priority. Here, in addition to chemical analyses, an active biomonitoring study using multiple biomarker responses in Nile tilapia Oreochromis niloticus was conducted to assess the effects of a contamination gradient along four reservoirs in Iguaçu River. Chemical analysis in the muscle showed high levels of metals in fish from the reservoir closest to an industrialized and environmentally degraded area, however fish exposed to all studied reservoirs showed hepatic alterations (necrosis and inflammatory processes). Also, significant variations of biochemical biomarkers were observed with no clear indication of contamination gradient, since an indicative of higher impact was found in an intermediary reservoir, including high concentrations of biliary polycyclic aromatic hydrocarbons (PAHs). However, nuclear morphological alterations (NMA) were less frequent at the same reservoir. Thus, the multi-biomarker approach allied to active biomonitoring is a practical and important tool to assess deleterious effects of contamination in freshwater, providing data for monitoring and conservation protocols.

Influence of Inert and Oxidizing Atmospheres on the Physical and Optical Properties of Luminescent Carbon Dots Prepared through Pyrolysis of a Model Molecule.

This work used L-tartaric acid as a model molecule to evaluate how the use of inert and oxidizing atmospheres during pyrolysis affected the physical and optical properties of the resulting carbon dots (CDs). Pyrolysis revealed to be a simple procedure that afforded CDs in a single step, dismissed the addition of organic solvents, and involved only one extraction stage that employed water. By X-ray diffraction a dependency between the structure of the CDs and the atmosphere (oxidizing or inert) used during the pyrolysis was found. Potentiometric titration demonstrated that the CDs were largely soluble in water; it also aided characterization of the various groups that contained sp(3) -hybridized carbon atoms on the surface of the dots. Raman spectroscopy suggested that different amounts of sp(2)- and sp(3)-hybridized carbon atoms emerged on the CDs depending on the pyrolysis atmosphere. In conclusion, the pyrolysis atmosphere influenced the physical properties, such as the composition and the final structure.

Rescuing a Troubled Tolcapone with PEGylated PLGA Nanoparticles: Design, Characterization, and Hepatotoxicity Evaluation.

Tolcapone is an orally active catechol-O-methyltransferase (COMT) inhibitor used as adjuvant therapy in Parkinson's disease. However, it has a highly hepatotoxic profile, as recognized by the U.S. Food and Drug Administration. As a possible solution, nanoscience brought us several tools in the development of new functional nanomaterials with tunable physicochemical properties, which can be part of a solution to solve several drawbacks, including drug's short half-life and toxicity. This work aims to use PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a stable carrier with lower hydrodynamic size and polydispersity to encapsulate tolcapone in order to overcome its therapeutic drawbacks. Using the nanoprecipitation method, tolcapone-loaded nanoparticles with a DLC% of 5.7% were obtained (EE% of 47.0%) and subjected to a lyophilization optimization process to obtain a final shelf-stable formulation. Six different cryoprotectants in concentrations up to 10% (w/v) were tested. A formulation of PLGA nanoparticles with 3% hydroxypropyl-ß-cyclodextrin (HPßCD) as a cryoprotectant (PLGA-HP@Tolc), presenting sub-200 nm sizes and low polydispersity (PdI < 0.200) was selected. Cytotoxicity assays, namely, MTT and SRB, were used to study the metabolic activity and cell density of tolcapone and PLGA-HP@Tolc-treated cells. In both assays, a hepatocarcinoma cell line (HepG2) growing in glucose or glucose-free media (galactose-supplemented medium) was used. The results demonstrated that the treatment with the PLGA-HP@Tolc formulation led to a decrease in cytotoxicity in comparison to free tolcapone-treated cells in both media tested. Moreover, the elected formulation also counteracted ATP-depletion and excessive ROS production induced by tolcapone. The results suggest that HPßCD might have a dual function in the formulation: cryoprotectant and anticytotoxic agent, protecting cells from tolcapone-induced damage. Using an in vitro COMT inhibition assay, the PLGA-HP@Tolc formulation demonstrated to inhibit COMT as efficiently as free tolcapone. Overall, the results suggest that tolcapone-loaded PLGA NPs could be an interesting alternative to free tolcapone, demonstrating the same in vitro efficacy in inhibiting COMT but with a safer cytotoxic profile.

Drug Development for Alzheimer's and Parkinson's Disease: Where Do We Go Now?

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases' progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors.

Development and internal validation of a clinical score to predict neonatal hypoglycaemia in women with gestational diabetes.

INTRODUCTION: Gestational diabetes (GD) is a risk factor for neonatal hypoglycaemia (NH), but other factors can increase this risk. OBJECTIVES: To create a score to predict NH in women with GD. METHODS: Retrospective study of women with GD with a live singleton birth between 2012 and 2017 from the Portuguese GD registry. Pregnancies with and without NH were compared. A logistic regression was used to study NH predictors. Variables independently associated with NH were used to score derivation. The model's internal validation was performed by a bootstrapping. The association between the score and NH was assessed by logistic regression. RESULTS: We studied 10216 pregnancies, 410 (4.0%) with NH. The model's AUC was 0.628 (95%CI: 0.599-0.657). Optimism-corrected c-index: 0.626. Points were assigned to variables associated with NH in proportion to the model's lowest regression coefficient: insulin-treatment 1, preeclampsia 3, preterm delivery 2, male sex 1, and small-for-gestational-age 2, or large-for-gestational-age 3. NH prevalence by score category 0-1, 2, 3, 4, and ≥5 was 2.3%, 3.0%, 4.5%, 6.0%, 7.4%, and 11.5%, respectively. Per point, the OR for NH was 1.35 (95% CI: 1.27-1.42). A score of 2, 3, 4, 5 or ≥6 (versus ≤1) had a OR for NH of 1.67 (1.29-2.15), 2.24 (1.65-3.04), 2.83 (2.02-3.98), 3.08 (1.83-5.16), and 6.84 (4.34-10.77), respectively. CONCLUSION: Per each score point, women with GD had 35% higher risk of NH. Those with ≥6 points had 6.8-fold higher risk of NH compared to a score ≤1. Our score may be useful for identifying women at a higher risk of NH.

Pilot of Outpatient Preoperative Evaluation Through Teleassistance.

The pilot project of pre-anesthetic evaluation through telemedicine at the Pedro Ernesto University Hospital (HUPE) of the State University of Rio de Janeiro (UERJ) is a commendable initiative that aims to address the challenges faced by patients in accessing preoperative care. The objective of this study was to reduce the waiting time between the surgical recommendation and its clinical clearance for the procedure. A service flow was established to enable patients to undergo a comprehensive evaluation, including examination and complementary tests, during a single visit with a general practitioner. Based on the type of surgery and the patient's comorbidities, the Teleconsultants Center assessed the case and provided the necessary guidance. A total of 20 patients were attended to in face-to-face sessions during morning shifts, with the participation of Internal Medicine and Anesthesiology. Subsequently, these patients' evaluations were scheduled for teleconsultation to assess their surgical risk. There has been a significant reduction in the time between the surgical recommendation and the clearance for the procedure with a notable improvement compared to the previous protocol. These initial outcomes demonstrate the project's potential to enhance the efficiency and effectiveness of the preoperative evaluation process through teleassistance.

Opiorphin as a biomarker of orofacial conditions: a meta-analysis.

The aim of this meta-analysis was to answer the following question: "Are there any differences in opiorphin biomarker concentrations between different orofacial conditions and controls?". Two reviewers searched for observational studies that evaluated the levels of opiorphin in orofacial conditions, annotated in seven main databases and three that compile gray literature. Of the 443 articles obtained initially, 8 met the inclusion criteria for quantitative analyses. Relative percentages showed a mean 24.1% higher opiorphin concentration in chronic conditions (Burning Mouth Syndrome, Oral Potentially Malignant Diseases and Temporomandibular Disorder) compared to controls; 33.2% higher opiorphin in sustained pain (Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis, Painful Oral Soft-tissue conditions); and 21.7% higher opiorphin after stimuli (Corneal Foreign Body, Capsaicin). Meta-analysis revealed a standardized mean difference of 0.62 [0.02, 1.22] in the absolute concentration of opiorphin in saliva for the chronic group compared to the control. The analogous values for the sustained group and the stimulated group were 2.24 [0.34, 4.14] and 0.43 [0.00, 0.85], respectively. No differences in opiorphin levels were found for 'after Local Anesthesia before Tooth Extraction' or for apicoectomy. Based on the available evidence, in general, a statistically higher level of opiorphin is found in orofacial conditions. Salivary opiorphin levels are elevated in chronic, persisted and acute pain conditions, presumably reflecting a physiological homeostatic adaptative response to different conditions such as stress or pain. Salivary opiorphin might therefore be used as a valuable biomarker in several oral disorders.

It takes two to remyelinate: A bioengineered platform to study astrocyte-oligodendrocyte crosstalk and potential therapeutic targets in remyelination.

The loss of the myelin sheath insulating axons is the hallmark of demyelinating diseases. These pathologies often lead to irreversible neurological impairment and patient disability. No effective therapies are currently available to promote remyelination. Several elements contribute to the inadequacy of remyelination, thus understanding the intricacies of the cellular and signaling microenvironment of the remyelination niche might help us to devise better strategies to enhance remyelination. Here, using a new in vitro rapid myelinating artificial axon system based on engineered microfibres, we investigated how reactive astrocytes influence oligodendrocyte (OL) differentiation and myelination ability. This artificial axon culture system enables the effective uncoupling of molecular cues from the biophysical properties of the axons, allowing the detailed study of the astrocyte-OL crosstalk. Oligodendrocyte precursor cells (OPCs) were cultured on poly(trimethylene carbonate-co-ε-caprolactone) copolymer electrospun microfibres that served as surrogate axons. This platform was then combined with a previously established tissue engineered glial scar model of astrocytes embedded in 1 % (w/v) alginate matrices, in which astrocyte reactive phenotype was acquired using meningeal fibroblast conditioned medium. OPCs were shown to adhere to uncoated engineered microfibres and differentiate into myelinating OL. Reactive astrocytes were found to significantly impair OL differentiation ability, after six and eight days in a co-culture system. Differentiation impairment was seen to be correlated with astrocytic miRNA release through exosomes. We found significantly reduction on the expression of pro-myelinating miRNAs (miR-219 and miR-338) and an increase in anti-myelinating miRNA (miR-125a-3p) content between reactive and quiescent astrocytes. Additionally, we show that OPC differentiation inhibition could be reverted by rescuing the activated astrocytic phenotype with ibuprofen, a chemical inhibitor of the small rhoGTPase RhoA. Overall, these findings show that modulating astrocytic function might be an interesting therapeutic avenue for demyelinating diseases. The use of these engineered microfibres as an artificial axon culture system will enable the screening for potential therapeutic agents that promote OL differentiation and myelination while providing valuable insight on the myelination/remyelination processes.

Critical Evaluation of Embedding Media for Histological Studies of Early Stages of Chick Embryo Development.

A histological examination is an important tool in embryology, developmental biology, and correlated areas. Despite the amount of information available about tissue embedding and different media, there is a lack of information regarding best practices for embryonic tissues. Embryonic tissues are considered fragile structures, usually small in size, and frequently challenging to position correctly in media for the subsequent histological steps. Here, we discuss the embedding media and procedures that provided us with appropriate preservation of tissue and easier orientation of embryos at early development. Fertilized Gallus gallus eggs were incubated for 72 h, collected, fixed, processed, and embedded with paraplast, polyethylene glycol (PEG), or historesin. These resins were compared by the precision of tissue orientation, the preview of the embryos in the blocks, microtomy, contrast in staining, preservation, average time, and cost. Paraplast and PEG did not allow correct embryo orientation, even with agar-gelatin pre-embedded samples. Additionally, structural maintenance was hindered and did not allow detailed morphological assessment, presenting tissue shrinkage and disruption. Historesin provided precise tissue orientation and excellent preservation of structures. Assessing the performance of the embedding media contributes significantly to future developmental research, optimizing the processing of embryo specimens and improving results.

Macrophage-based therapy for intervertebral disc herniation: preclinical proof-of-concept.

Intervertebral disc (IVD) degeneration and herniation is a leading cause of disability globally and a large unmet clinical need. No efficient non-surgical therapy is available, and there is an urgency for minimally invasive therapies capable of restoring tissue function. IVD spontaneous hernia regression following conservative treatment is a clinically relevant phenomenon that has been linked to an inflammatory response. This study establishes the central role of macrophages in IVD spontaneous hernia regression and provides the first preclinical demonstration of a macrophage-based therapy for IVD herniation. A rat model of IVD herniation was used to test complementary experimental setups: (1) macrophage systemic depletion via intravenous administration of clodronate liposomes (Group CLP2w: depletion between 0 and 2 weeks post-lesion; Group CLP6w: depletion between 2 and 6 weeks post-lesion), and (2) administration of bone marrow-derived macrophages into the herniated IVD, 2 weeks post-lesion (Group Mac6w). Herniated animals without treatment were used as controls. The herniated area was quantified by histology in consecutive proteoglycan/collagen IVD sections at 2 and 6 weeks post-lesion. Clodronate-mediated macrophage systemic depletion was confirmed by flow cytometry and resulted in increased hernia sizes. Bone marrow-derived macrophages were successfully administered into rat IVD hernias resulting in a 44% decrease in hernia size. No relevant systemic immune reaction was identified by flow cytometry, cytokine, or proteomic analysis. Furthermore, a possible mechanism for macrophage-induced hernia regression and tissue repair was unveiled through IL4, IL17a, IL18, LIX, and RANTES increase. This study represents the first preclinical proof-of-concept of macrophage-based immunotherapy for IVD herniation.

Long non-coding RNA H19 regulates matrisome signature and impacts cell behavior on MSC-engineered extracellular matrices.

BACKGROUND: The vast and promising class of long non-coding RNAs (lncRNAs) has been under investigation for distinct therapeutic applications. Nevertheless, their role as molecular drivers of bone regeneration remains poorly studied. The lncRNA H19 mediates osteogenic differentiation of Mesenchymal Stem/Stromal Cells (MSCs) through the control of intracellular pathways. However, the effect of H19 on the extracellular matrix (ECM) components is still largely unknown. This research study was designed to decode the H19-mediated ECM regulatory network, and to reveal how the decellularized siH19-engineered matrices influence MSC proliferation and fate. This is particularly relevant for diseases in which the ECM regulation and remodeling processes are disrupted, such as osteoporosis. METHODS: Mass spectrometry-based quantitative proteomics analysis was used to identify ECM components, after oligonucleotides delivery to osteoporosis-derived hMSCs. Moreover, qRT-PCR, immunofluorescence and proliferation, differentiation and apoptosis assays were performed. Engineered matrices were decellularized, characterized by atomic force microscopy and repopulated with hMSC and pre-adipocytes. Clinical bone samples were characterized by histomorphometry analysis. RESULTS: Our study provides an in-depth proteome-wide and matrisome-specific analysis of the ECM proteins controlled by the lncRNA H19. Using bone marrow-isolated MSC from patients with osteoporosis, we identified fibrillin-1 (FBN1), vitronectin (VTN) and collagen triple helix repeat containing 1 (CTHRC1), among others, as having different pattern levels following H19 silencing. Decellularized siH19-engineered matrices are less dense and have a decreased collagen content compared with control matrices. Repopulation with naïve MSCs promotes a shift towards the adipogenic lineage in detriment of the osteogenic lineage and inhibits proliferation. In pre-adipocytes, these siH19-matrices enhance lipid droplets formation. Mechanistically, H19 is targeted by miR-29c, whose expression is decreased in osteoporotic bone clinical samples. Accordingly, miR-29c impacts MSC proliferation and collagen production, but does not influence ALP staining or mineralization, revealing that H19 silencing and miR-29c mimics have complementary but not overlapping functions. CONCLUSION: Our data suggest H19 as a therapeutic target to engineer the bone ECM and to control cell behavior.

Enamel properties after tooth bleaching with hydrogen/carbamide peroxides in association with a CPP-ACP paste.

BACKGROUND: This study evaluated the impact of bleaching teeth using blends of a CPP-ACP paste (MI Paste; MI) and carbamide/hydrogen peroxides in different proportions on surface properties of bleached enamel. METHODS: Ninety bovine incisors were bleached with 7.5% hydrogen peroxide (HP), 16% carbamide peroxide (CP), MI and blends of HP or CP:MI at three proportions (1:1, 2:1, 1:2). Hardness and roughness were measured at baseline and after bleaching. Enamel morphology was evaluated by Scanning Electron Microscopy (SEM). The data were analyzed by two-way ANOVA for repeated measurements and Tukey's test. RESULTS: Most of the samples bleached with MI in combination with peroxides presented increased hardness and roughness which were associated to mineral deposition, as observed by SEM images. Blends with higher fractions of MI did not offer superior benefits. CONCLUSIONS: The use of a CPP-ACP paste mixed to carbamide/hydrogen peroxides can decrease adverse side-effects from tooth bleaching on an enamel surface.

Antiparasitic potential of agrochemical fungicides on a non-target aquatic model (Daphnia × Metschnikowia host-parasite system).

Pesticides are a major anthropogenic threat to the biodiversity of freshwater ecosystems, having the potential to affect non-target aquatic organisms and disrupt the processes in which they intervene. Important knowledge gaps have been recognised concerning the ecological effects of synthetic fungicides on non-target symbiotic aquatic fungi and the ecological processes where they intervene. The goal of this work was to assess the influence of three commonly used fungicides (myclobutanil, metalaxyl and cymoxanil), which differ in their mode of action, on a host (the crustacean Daphnia magna) × parasite (the yeast Metschnikowia bicuspidata) experimental model. Using a set of life history experiments, we evaluated the effect of each fungicide on the outcome of this relationship (disease) and on the fitness of both host and parasite. Contrasting results were observed: (i) cymoxanil and metalaxyl were overall innocuous to host and parasite at the tested concentrations, although host reproduction was occasionally reduced in the simultaneous presence of parasite and fungicide; (ii) on the contrary, myclobutanil displayed a clear antifungal effect, decreasing parasite prevalence and alleviating infection signs in the hosts. This antiparasitic effect of myclobutanil was further investigated with a follow-up experiment that manipulated the timing of application of the fungicide, to understand which stage of parasite development was most susceptible: while myclobutanil did not interfere in the early stages of infection, its antifungal activity was clearly observable at a later stage of the disease (by impairing the production of transmission stages of the parasite). More research is needed to understand the broader consequences of this parasite-clearance effect, especially in face of increasing evidence that parasites are ecologically more important than their cryptic nature might suggest.

Tannin-based coagulants: Current development and prospects on synthesis and uses.

Population growth, industrialization, urbanization, and agriculture lead to a decrease in the availability of clean water. Coagulation/flocculation is one of the most common operations in water, urban wastewater, and industrial effluents treatment systems. Usually, this process is achieved using conventional coagulants that have their performance affected by pH, are poorly biodegradable, produce a huge volume of sludge, and are associated with degenerative diseases. As a substitute for these chemicals, natural coagulants have been highly researched for the last ten/fifteen years, especially the tannin-based (TB) ones. This review paper highlights the advantages of using these greener products to treat different types of water, wastewater, and effluents, especially from dairy, cosmetics, laundries, textile, and other industries. TB coagulants can successfully remove turbidity, color, suspended solids, soluble organic (chemical/biochemical oxygen demand) and inorganic matter (total phosphate, and heavy metals), and microorganisms. TB coagulants are compatible with other treatment technologies and can be used as coagulant-aid to reduce the consumption of chemicals. TB coagulants can reduce operating costs of water treatment due to less alkalinity consumption, as pH adjustment is sometimes unnecessary, and the production of a smaller volume of biodegradable sludge. TB coagulants can be synthesized by valorizing wastes/by-products, from the bark of some specific trees and skins/pomace of different fruits and vegetables. The strengths, weaknesses, opportunities, and threats (SWOT) on TB coagulants are discussed. The progress of TB coagulants is promising, but some threats should be overcome, especially on tannin extraction and cationization. The market competition with conventional coagulants, the feasibility of application in real waters, and the reluctance of the industries to adapt to new technologies are other weaknesses to be surpassed.