Is the injection of tramadol effective at control of pain after impacted mandibular third molar extractions? A systematic review and meta-analysis.

BACKGROUND: Third molar extraction is among the most common surgical procedures performed by oral-maxillofacial surgeons. Postoperative pain, swelling and trismus are common, especially in wisdom teeth, due to trauma to local tissues and the duration of the surgical procedure, among other factors. MATERIAL AND METHODS: This systematic review was conducted in accordance with the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' in order to answer the focused question: 'Is the local submucosal injection of tramadol effective at the control of postoperative pain in patients submitted to impacted mandibular third molar extractions?'. We analyzed papers published until March 30, 2021 in the MEDLINE|PubMed, Web of Science and Cochrane Library databases. Gray literature was also consulted. Standard pairwise meta-analyses of direct comparisons were performed using a fixed-effect model; I2 ≥ 50 % or ≥ 75 % indicated moderate or high heterogeneity, respectively. Risk of bias was assessed by Cochrane Collaboration's tool. RESULTS: In total, 172 participants (98 males and 74 females, aged 18 or over) from three randomized placebo-controlled trials were considered for analysis. The submucosal injection of 2 ml of tramadol adjacent to the impacted mandibular third molar was effective in controlling pain up to 6-hours after surgery, in increasing the onset of consumption of rescue analgesic and in reducing the total number of rescue analgesics used. CONCLUSIONS: The submucosal injection of tramadol can be considered a safe and effective procedure for pain control after impacted mandibular third molar extractions.

Short communication: Anesthetic residues in milk after topical application during treatment of hoof lesions in dairy cows.

Hoof lesions in dairy cows are usually treated by trimming the hoof. However, trimming by itself can cause severe pain or exacerbate already existing pain. Hoof trimming is usually not carried out by trained veterinarians, and pain management is not provided. Pain control during trimming is not only an ethical obligation but also allows for better manipulation and more meticulous treatment. Tri-Solfen (Bayer Animal Health, Pymble, Australia) is a spray gel containing lidocaine, bupivacaine, and cetrimide that is easily applied topically and has demonstrated pain-mitigation effects during and after hoof trimming. In the European Union, these local anesthetics are not approved for use in food-producing animals because of a lack of residue data and concerns about genotoxic effects in cattle and humans. The aim of this study was to assess lidocaine, bupivacaine, and 2,6-xylidine residues in milk after Tri-Solfen application in dairy cows. Five dairy cattle in the dry-off period were enrolled in the study based on clinical evidence of lameness (score ≥3 on a 5-point scale). After cleaning and superficial trimming, we applied 3 to 14 mL of Tri-Solfen to the lesions before continuing treatment. Two milk samples were collected per animal in the following 4 milkings and analyzed in a reference laboratory. Residues of lidocaine above the limits of quantification (0.2 µg/L) were found in milk samples in the first milking 6 h after treatment in only 2 cows. This study shows that excretion of local anesthetics and their metabolites in milk after topical application of Tri-Solfen is negligible and even undetectable after the first milking 6 h post-treatment.

Use of topical local anesthetics to control pain during treatment of hoof lesions in dairy cows.

Hoof pathologies in dairy cows have a major effect on both production and animal welfare. Trimming of excess or diseased hoof tissue is essential for the treatment of many of these conditions. Trimming hoof lesions can cause severe pain, resulting in adverse behavioral responses with risk for animal and human safety. Interventions are usually carried out by nonveterinary technicians in the absence of pain management training. Pain control during trimming is not only an ethical obligation but also allows for better manipulation and more meticulous treatment. The aim of this study was to test the efficacy of Tri-Solfen (Bayer Australia Ltd., Pymble, NSW, Australia), a combination of local anesthetics in a topical gel form, containing lidocaine, bupivacaine, adrenaline, and cetrimide, for the treatment of pain associated with trimming of hoof lesions. Sixty-two Holstein-Frisian cows were selected for trimming at the drying-off period and were visually scored for lameness before entering the chute. After diagnosis of the hoof lesion but before deep trimming was initiated, each animal was randomly distributed to 2 groups: C, usual trimming with no pain control, and T, trimming with a local anesthetic formulation being applied immediately after live corium was exposed. During curative trimming, behavior observation was conducted by 2 observers blind to treatment. In 27 cows, algometry measurements were performed before and after the procedure to assess animal reaction to pressure. Lameness scoring was again performed as the cow left the chute. Nonparametric tests and ANOVA were performed. Results showed that use of the topical anesthetic formulation significantly reduced reaction to trimming and lameness score after trimming when compared with nontreated animals. Algometry values showed increased pressure threshold after application of topical anesthetics. This study suggests that the use of topical local anesthesia with lidocaine and bupivacaine helps reduce pain associated with corrective trimming of severe hoof lesions, enhancing animal welfare and potentially ensuring safety of trimmers.

Analysis of genetic diversity of Laeliinae (Orchidaceae) in the State of Sergipe using ISSR markers.

The Orchidaceae represent one of the largest and most diverse families on the planet. However, this family is constantly threatened by predators and by the advancement of urban centers over its natural habitats. The objective of this study was to use inter-simple sequence repeat markers to evaluate the genetic diversity between orchid accessions of the Laeliinae subtribe, which comprise part of the Orchidaceae study collection at the Department of Agronomic Engineering of the Federal University of Sergipe. DNA was extracted from each specimen by using an adapted 2% cetyltrimethyl ammonium bromide protocol. Similarity between individuals was calculated using the Jaccard method. Clustering was carried out by the unweighted pair group method with arithmetic mean method, with resampling and 10,000 bootstraps. Eighty-seven fragments were obtained, all of which were polymorphic, revealing high variability between accessions. The mean similarity was 35.77% between Encyclia sp individuals, and 35.90% between specimens of Cattleya tigrina. For Epidendrum secundum, a relationship between geographic and genetic distances was observed, and the accession collected in the southern part of the State of Sergipe (Serra de Itabaiana National Park) was more divergent than that of the other parts of the state. The data generated in this study will guide further research aimed at the ex situ conservation of these materials.

Extracellular enzymatic profiles and taxonomic identification of endophytic fungi isolated from four plant species.

Plants of medicinal and economic importance have been studied to investigate the presence of enzyme-producing endophytic fungi. The characterization of isolates with distinct enzyme production potential may identify suitable alternatives for specialized industry. At Universidade Estadual de Maringá Laboratory of Microbial Biotechnology, approximately 500 isolates of endophytic fungi have been studied over the last decade from various host plants, including medicinally and economically important species, such as Luehea divaricata (Martius et Zuccarini), Trichilia elegans A. Juss, Sapindus saponaria L., Piper hispidum Swartz, and Saccharum spp. However, only a fraction of these endophytes have been identified and evaluated for their biotechnological application, having been initially grouped by morphological characteristics, with at least one representative of each morphogroup tested. In the current study, several fungal strains from four plants (L. divaricata, T. elegans, S. saponaria, and Saccharum spp) were identified by ribosomal DNA typing and evaluated semi-quantitatively for their enzymatic properties, including amylase, cellulase, pectinase, and protease activity. Phylogenetic analysis revealed the presence of four genera of endophytic fungi (Diaporthe, Saccharicola, Bipolaris, and Phoma) in the plants examined. According to enzymatic tests, 62% of the isolates exhibited amylase, approximately 93% cellulase, 50% pectinase, and 64% protease activity. Our results verified that the composition and abundance of endophytic fungi differed between the plants tested, and that these endophytes are a potential enzyme production resource of commercial and biotechnological value.

Insulin therapy modulates mitochondrial dynamics and biogenesis, autophagy and tau protein phosphorylation in the brain of type 1 diabetic rats.

The main purpose of this study was to examine whether streptozotocin (STZ)-induced type 1 diabetes (T1D) and insulin (INS) treatment affect mitochondrial function, fission/fusion and biogenesis, autophagy and tau protein phosphorylation in cerebral cortex from diabetic rats treated or not with INS. No significant alterations were observed in mitochondrial function as well as pyruvate levels, despite the significant increase in glucose levels observed in INS-treated diabetic rats. A significant increase in DRP1 protein phosphorylated at Ser616 residue was observed in the brain cortex of STZ rats. Also an increase in NRF2 protein levels and in the number of copies of mtDNA were observed in STZ diabetic rats, these alterations being normalized by INS. A slight decrease in LC3-II levels was observed in INS-treated rats when compared to STZ diabetic animals. An increase in tau protein phosphorylation at Ser396 residue was observed in STZ diabetic rats while INS treatment partially reversed that effect. Accordingly, a modest reduction in the activation of GSK3ß and a significant increase in the activity of phosphatase 2A were found in INS-treated rats when compared to STZ diabetic animals. No significant alterations were observed in caspases 9 and 3 activity and synaptophysin and PSD95 levels. Altogether our results show that mitochondrial alterations induced by T1D seem to involve compensation mechanisms since no significant changes in mitochondrial function and synaptic integrity were observed in diabetic animals. In addition, INS treatment is able to normalize the alterations induced by T1D supporting the importance of INS signaling in the brain.

Genotoxic and biochemical changes in Baccharis trimera induced by coal contamination.

The processing and combustion of coal in thermal power plants release anthropogenic chemicals into the environment. Baccharis trimera is a common plant used in folk medicine that grows readily in soils degraded by coal mining activities. This shrub bioaccumulates metals released into the environment, and thus its consumption may be harmful to health. The purpose of this study was to investigate the phytochemical profile, antioxidant capacity (DPPH), genotoxic (comet assay) and mutagenic potential (CBMN-cyt) in V79 cells of B. trimera aqueous extracts in the coal-mining region of Candiota (Bt-AEC), and in Bagé, a city that does not experience the effects of exposure to coal (Bt-AEB, a reference site). In the comet assay, only Bt-AEC was genotoxic at the highest doses (0.8mg/mL and 1.6mg/mL), compared to the control. For extracts from both areas, mutagenic effects were observed at higher concentrations compared to the control. The cell damage parameters were significantly high in both extracts; however, more striking values were observed for Bt-AEC, up to the dose of 0.8mg/mL. In chemical analysis, no variation was observed in the contents of flavonoids and phenolic compounds, neither the antioxidant activity, which may suggest that DNA damage observed in V79 cells was induced by the presence of coal contaminants absorbed by the plant.

Vascular Mechanisms of Post-exercise Blood Pressure Responses in Peripheral Artery Disease.

This study aimed to analyze the vascular mechanisms involved in post-resistance decreases in blood pressure in patients with peripheral artery disease. 17 patients underwent 2 experimental sessions conducted in random order: resistance exercise (REx-3×10 reps in 8 exercises with intensity of ~ 60% of 1 RM) and control (C- resting on the exercise machines for 50 min). Before and after each experimental session, blood pressure, reflected wave indicators, pulse wave velocity, blood flow, blood flow post-reactive hyperemia and peripheral vascular resistance responses were obtained. Both sessions increased brachial systolic, diastolic and mean blood pressure (greatest increase REx: 11 mmHg; greatest increase C: 19 mmHg; P<0.01); however, the increases were greater after the C session (P<0.01). Reflected wave indicators increased only after the C session (P<0.06), while pulse wave velocity increased similarly after both sessions (P=0.66). Individual analyses indicated a large variability between patients in vascular variables responses. A single bout of REx decreased blood pressure in peripheral artery disease patients, and these responses were followed by changes in reflected wave indicators. The other factors presented high individual variability, and thus it was not possible to identify specific factors associated with blood pressure reduction in peripheral artery disease patients.

Crosstalk between diabetes and brain: glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration.

According to World Health Organization estimates, type 2 diabetes (T2D) is an epidemic (particularly in under development countries) and a socio-economic challenge. This is even more relevant since increasing evidence points T2D as a risk factor for Alzheimer's disease (AD), supporting the hypothesis that AD is a "type 3 diabetes" or "brain insulin resistant state". Despite the limited knowledge on the molecular mechanisms and the etiological complexity of both pathologies, evidence suggests that neurodegeneration/death underlying cognitive dysfunction (and ultimately dementia) upon long-term T2D may arise from a complex interplay between T2D and brain aging. Additionally, decreased brain insulin levels/signaling and glucose metabolism in both pathologies further suggests that an effective treatment strategy for one disorder may be also beneficial in the other. In this regard, one such promising strategy is a novel successful anti-T2D class of drugs, the glucagon-like peptide-1 (GLP-1) mimetics (e.g. exendin-4 or liraglutide), whose potential neuroprotective effects have been increasingly shown in the last years. In fact, several studies showed that, besides improving peripheral (and probably brain) insulin signaling, GLP-1 analogs minimize cell loss and possibly rescue cognitive decline in models of AD, Parkinson's (PD) or Huntington's disease. Interestingly, exendin-4 is undergoing clinical trials to test its potential as an anti-PD therapy. Herewith, we aim to integrate the available data on the metabolic and neuroprotective effects of GLP-1 mimetics in the central nervous system (CNS) with the complex crosstalk between T2D-AD, as well as their potential therapeutic value against T2D-associated cognitive dysfunction.

Mitochondrial quality control systems sustain brain mitochondrial bioenergetics in early stages of type 2 diabetes.

Mitochondria have a crucial role in the supply of energy to the brain. Mitochondrial alterations can lead to detrimental consequences on the function of brain cells and are thought to have a pivotal role in the pathogenesis of several neurologic disorders. This study was aimed to evaluate mitochondrial function, fusion-fission and biogenesis and autophagy in brain cortex of 6-month-old Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes (T2D). No statistically significant alterations were observed in mitochondrial respiratory chain and oxidative phosphorylation system. A significant decrease in the protein levels of OPA1, a protein that facilitates mitochondrial fusion, was observed in brain cortex of GK rats. Furthermore, a significant decrease in the protein levels of LC3-II and a significant increase in protein levels of mTOR phosphorylated at serine residue 2448 were observed in GK rats suggesting a suppression of autophagy in diabetic brain cortex. No significant alterations were observed in the parameters related to mitochondrial biogenesis. Altogether, these results demonstrate that during the early stages of T2D, brain mitochondrial function is maintained in part due to a delicate balance between mitochondrial fusion-fission and biogenesis and autophagy. However, future studies are warranted to evaluate the role of mitochondrial quality control pathways in late stages of T2D.

Asymmetric magnetoimpedance in exchange-biased systems.

Magnetic systems with competing anisotropies generally exhibit asymmetry between the maximum amplitudes of the right and left maxima in a magnetoimpedance curve. Small errors in positioning the samples at the experimental setup may also produce such asymmetry. In this work, we present a study on the sources of the asymmetry between magnetoimpedance peaks in systems that present the exchange bias phenomenon, by comparing a phenomenological model to experimental data. A set of samples with different repetitions of the NiFe/FeMn exchange-biased bilayer was used in this study. From the frequency evolution of the asymmetry, together with magnetization curves, we were able to identify the sources for the observed magnetoimpedance asymmetry found on our experimental data.

Root deformation affects mineral nutrition but not leaf gas exchange and growth of Genipa americana seedlings during the recovery phase after soil flooding.

Root deformation (RD) caused by errors in the pricking out process are irreversible and very difficult to detect in container-grown seedlings at the time of planting in the field. The objective of this study was to evaluate the effects of RD on leaf gas exchange, growth, biomass allocation and mineral nutrition of G. americana seedlings during the recovery phase after soil flooding. Four-months-old seedlings, with and without RD, were flooded for 42 days and their recovery was evaluated 28 days after soil drainage. There were no significant interactions between RD and soil flooding for all leaf gas exchange, growth and mineral nutrition after soil drainage, with the exception of leaf P concentrations. In plants with no RD, the P concentration in leaves of non-flooded plants was significantly higher than that of plants with RD. Soil flooding and RD did not influence leaf or root N concentrations or whole-plant N content. RD increased the K concentration in the roots, but not in the leaves. Changes in the nutrient concentrations in leaves and roots indicate that RD may affect physiological performance of seedlings after planting in the field.

Is there an association between the use of antidepressants and complications involving dental implants? A systematic review and meta-analysis.

The aim of this systematic review was to evaluate published evidence on the association between the use of antidepressants and complications involving dental implants. Two reviewers independently performed electronic searches of the MEDLINE/PubMed, Cochrane Library, and Scopus databases for relevant articles published up to May 30, 2019. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for the appraisal of the methodological quality of the studies included. A meta-analysis was performed to determine the risk of dental implant failure in individuals taking antidepressants. Five comparative observational studies were selected for this review; these included a total of 2056 participants with 5302 implants. The results suggest a risk ratio of 3.73 (95% confidence interval 1.85-7.52, P=0.0002) for implant failure in antidepressant users submitted to oral rehabilitation when compared to non-users. However, these studies did not present methodological rigour or standardize the drugs used. Thus, there is insufficient evidence for an association between antidepressant use and dental implant complications.

Peripheral neuropathy in patients with primary antiphospholipid (Hughes') syndrome.

The involvement of the peripheral nervous system in diverse autoimmune diseases is well established. However, no appropriately designed studies have been performed in primary antiphospholipid syndrome (PAPS)-related peripheral neuropathy. We aimed to investigate the occurrence of peripheral neuropathy in patients diagnosed with PAPS. Twenty-six consecutive patients with PAPS (Sapporo criteria) and 20 age- and gender-matched healthy controls were enrolled at two referral centers. Exclusion criteria were secondary causes of peripheral neuropathy. A complete clinical neurologic exam followed by nerve conduction studies (NCS) was performed. Paresthesias were reported in eight patients (31%). Objective mild distal weakness and abnormal symmetric deep tendon reflexes were observed in three patients (11.5%). With regard to the electrophysiologic evidence of peripheral neuropathy, nine patients (35.0%) had alterations: four (15.5%) had pure sensory or sensorimotor distal axonal neuropathy (in two of them a carpal tunnel syndrome was also present) and one (4%) had sensorimotor demyelinating and axonal neuropathy involving upper and lower extremities, while four patients (15.5%) showed isolated carpal tunnel syndrome. Clinical and serologic results were similar in all the patients with PAPS, regardless of the presence of electrophysiologic alterations. In conclusion, peripheral neuropathy is a common asymptomatic abnormality in patients with PAPS. The routine performance of NCS may be considered when evaluating such patients.

Methodology for radionuclides quantification through "in vitro" bioassay.

In Brazil, the radionuclides used for therapy are: (131)I, (153)Sm, (90)Y and (177)Lu, both for routine or research protocols. The radionuclide activity excreted by patients may be quantified by bioassay analysis and constitutes a powerful tool for individual treatment planning. The Bioassay Laboratory (LBIOVT) of the Institute of Radiation Protection and Dosimetry (IRD) has equipments for gamma and beta spectroscopy. These systems are calibrated in energy and efficiency using reference sources supplied by the National Laboratory of Radiation Metrology (LMNRI/IRD). The LBIOVT has operational procedures according ISO-ABNT-17025 recommendations and participates of international and national intercomparisons. The patient samples are collected immediately after radiopharmaceutical administrations, at the hospital or at the patient residence, and are handled, stored and transported according national radiation protection regulations. The radionuclide specific activity (Bq/L) is referenced to date and time of excretion, for the estimation of the individual biological half-live. The volume of excreta may carefully manipulated in order to avoid losses and misinterpretation in the activity quantification. The process of the LBIOVT accreditation and its participation in intercomparisons may guarantee the confidence of the results, allowing the minimization of the uncertainties in the individual monitoring.

Exercise training associated with diet improves heart rate recovery and cardiac autonomic nervous system activity in obese children.

The purpose of this study was to test the hypotheses that in obese children: 1) hypocaloric diet (D) improves both heart rate recovery at 1 min (Δ HRR1) cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in obese children; 2) Diet and exercise training (DET) combined leads to greater improvement in both Δ HRR1 after an exercise test and in CANSA, than D alone. Moreover, we examined the relationships among Δ HRR1, CANSA, cardiorespiratory fitness and anthropometric variables (AV) in obese children submitted to D and to DET. 33 obese children (10 ± 0.2 years; body mass index (BMI) >95 (th) percentile) were divided into 2 groups: D (n=15; BMI=31 ± 1 kg/m²)) and DET (n=18; 29 ± 1 kg/m²). All children performed a maximal cardiopulmonary exercise test on a treadmill. The Δ HRR1 or LF/HF ratio (P>0.05). In contrast, the DET group showed increased peak VO2 ( P=0.01) and improved Δ HRR1 (Δ HRR1=37.3 ± 2.6; P=0.01) and LF/HF ratio ( P=0.001). The DET group demonstrated significant relationships among Δ HRR1, peak VO2 and CANSA (P<0.05). In conclusion, DET, in contrast to D, promoted improved ÄΔ HRR1 and CANSA in obese children, suggesting a positive influence of increased levels of cardiorespiratory fitness by exercise training on cardiac autonomic activity.

Evaluation of blockbuster drugs under the rule-of-five.

The current drug research techniques, combinatorial synthesis and high throughput screening, enabled the obtaining and pre-evaluation of thousands of compounds in short time. In order to chose the best hits to become leads, observation of drug-likeness tries to optimize this selection. Probably, the most widely used filter is Lipinski's Rule-of-five, which proposes that molecules with poor permeation and oral absorption have molecular weight > 500, Clog P > 5, hydrogen-bond donor > 5 and hydrogen-bond acceptor > 10. In order to evaluate the Rule-of-five, the top pharmaceutical products in 2007 were analyzed. Among 60 drugs, 7 (atorvastatin, montelukast, docetaxel, telmisartan, tacrolimus, leuprolide and olmesartan) did not fit the rule, and 5 failed only one of the threshold values. It was possible to conclude that the rule is very useful to select better compounds in chemolibraries, but it must be used carefully and with criteria, to avoid a possible exclusion of promising compounds.

Synaptic vesicle protein trafficking at the glutamate synapse.

Expression of the integral and associated proteins of synaptic vesicles is subject to regulation over time, by region, and in response to activity. The process by which changes in protein levels and isoforms result in different properties of neurotransmitter release involves protein trafficking to the synaptic vesicle. How newly synthesized proteins are incorporated into synaptic vesicles at the presynaptic bouton is poorly understood. During synaptogenesis, synaptic vesicle proteins sort through the secretory pathway and are transported down the axon in precursor vesicles that undergo maturation to form synaptic vesicles. Changes in protein content of synaptic vesicles could involve the formation of new vesicles that either mix with the previous complement of vesicles or replace them, presumably by their degradation or inactivation. Alternatively, new proteins could individually incorporate into existing synaptic vesicles, changing their functional properties. Glutamatergic vesicles likely express many of the same integral membrane proteins and share certain common mechanisms of biogenesis, recycling, and degradation with other synaptic vesicles. However, glutamatergic vesicles are defined by their ability to package glutamate for release, a property conferred by the expression of a vesicular glutamate transporter (VGLUT). VGLUTs are subject to regional, developmental, and activity-dependent changes in expression. In addition, VGLUT isoforms differ in their trafficking, which may target them to different pathways during biogenesis or after recycling, which may in turn sort them to different vesicle pools. Emerging data indicate that differences in the association of VGLUTs and other synaptic vesicle proteins with endocytic adaptors may influence their trafficking. These observations indicate that independent regulation of synaptic vesicle protein trafficking has the potential to influence synaptic vesicle protein composition, the maintenance of synaptic vesicle pools, and the release of glutamate in response to changing physiological requirements.

Socio-demographic and perceived environmental correlates of walking in Portuguese adults--a multilevel analysis.

Several studies have identified associations between walking levels and socio-demographic and environmental variables. The aim of the present study was to describe walking patterns and examine associations between socio-demographic characteristics and perceived environmental attributes with walking among adults living in the Azorean Archipelago (Portugal). In all, 7330 adult participants (4104 women), aged 38.1 +/- 9.3 years, of the 2004 Azorean Physical Activity and Health Study answered the Environmental Module and the short version of the International Physical Activity Questionnaire. Among the Azoreans, the environmental dimension "infrastructures, access to destinations, social environment and aesthetics" and moderate to vigorous physical activity were positively associated with walking levels; and smoking, sitting time and being married were negatively related, regardless of gender, age or education level. Through the cross-sectional nature of this study, our results suggest that targeted programs for Azoreans aimed to increase walking levels should consider that infrastructures, access to destinations, social environment and aesthetics seem to act synergistically and associate positively with walking behaviour.