Type 2 and type 3 innate lymphoid cells at the maternal-fetal interface: implications in preterm birth.

BACKGROUND: Preterm birth (PTB) is one of the major causes of neonatal morbidity and mortality worldwide. It is commonly accepted that the act of giving birth is the final step in a proinflammatory signaling cascade, orchestrated by an intrauterine milieu coupled to hormonal cues. Consequently, the inflammatory process plays a pivotal role during the pathogenesis of human labor, both in term and preterm deliveries. The ability of innate lymphoid cells (ILCs) to act as pro-inflammatory mediators arose the interest to study their role in normal and pathological pregnancies. The aim of this work was to analyze the relative frequencies of ILCs subsets in pregnancy and the levels of IL-4, IL-17, IL-22, and IFN-γ as inflammatory mediators. Accordingly, we hypothesized that changes in the proportions of ILCs subpopulations could be related to preterm birth. METHODS: We analyzed 15 full-term delivery samples and six preterm delivery samples. In the full-term group (FTB) peripheral blood was taken during routine blood analysis, on 3 occasions: 1st, 2nd and 3rd trimester. After delivery, peripheral blood, cord blood and placenta were collected. In PTB group, peripheral blood samples were obtained on two occasions: before and 24 h after treatment with progesterone. We used flow cytometry to analyze ILCs in maternal peripheral blood, placenta, and cord blood samples. Maternal peripheral blood and cord blood samples were analyzed by enzyme-linked immunosorbent assay for IL-4, IL-17, IL-22, and IFN-γ plasma levels at the time of labor. RESULTS: We observed significantly increased relative frequencies of ILC2 and ILC3 in the decidua, as well as an increase of ILC2 in cord blood samples in PTB group, compared to FTB samples. We also found a decrease in IFN-γ in peripheral blood samples of the PTB group, suggesting a functional withdrawal. Additionally, IL-4, IL-17, IL-22 levels were similar in PTB and FTB groups, denoting a relevant role in mediating labor. CONCLUSION: Our results suggest that ILC2 and ILC3 play a role in PTB by mediating an inflammatory response. Further work is necessary to evaluate the importance of ILCs in the regulation of labor.

Highly sensitive screening and analytical characterization of synthetic cannabinoids in nine different herbal mixtures.

The popularity of new psychoactive substances among drug users has become a public health concern worldwide. Among them, synthetic cannabinoids (SCs) represent the largest, most diversified and fastest growing group. Commonly known as 'synthetic marijuana' as an alternative to cannabis, these synthetic compounds are easily accessible via the internet and are sold as 'herbal incenses' under different brand names with no information about the chemical composition. In the present work, we aim to integrate gas chromatography-tandem mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) data as useful strategy for the identification and confirmation of synthetic cannabinoids present in nine seized herbal incenses. The analysis of all samples allowed the initial identification of 9 SCs, namely 5 napthoylindoles (JWH-018, JWH-073, JWH-122, JWH-210, MAM-2201), APINACA, XLR-11 and CP47,497-C8 and its enantiomer. JWH-018 was the most frequently detected synthetic compound (8 of 9 samples), while APINACA and XLR-11 were only identified in one herbal product. Other non-cannabinoid drugs, including oleamide, vitamin E and vitamin E acetate, have also been detected. Oleamide and vitamin E are two adulterants, frequently added to herbal products to mask the active ingredients or added as preservatives. However, to our knowledge, no analytical data about vitamin E acetate was reported in herbal products, being the first time that this compound is identified on this type of samples. The integration data obtained from the used analytical technologies proved to be useful, allowing the preliminary identification of the different SCs in the mixture. Furthermore, the examination of mass spectral fragment ions, as well as the results of both 1D and 2D NMR experiments, enabled the identification and confirmation of the molecular structure of SCs.

Relationship between Volatile Composition and Bioactive Potential of Vegetables and Fruits of Regular Consumption-An Integrative Approach.

In recent years, there has been a growing interest in studying and exploring the potential health benefits of foods, mainly from vegetables and fruits from regular intake. The presence of secondary metabolites, namely polyphenols, carotenoids and terpenes, in certain food matrices seems to contribute to their functional properties, expressed through an increased prevention in the development of certain chronic diseases, namely coronary heart diseases, neurodegenerative diseases, cancer and diabetes. However, some foods' volatile secondary metabolites also present important bioactive properties, although this is a poorly scientifically explored field. In this context, and in order to explore the potential bioactivity of volatile metabolites in different vegetables and fruits from regular consumption, the volatile composition was established using a green extraction technique, solid phase microextraction in headspace mode (HS-SPME), combined with gas chromatography tandem mass spectrometry (GC-MS). A total of 320 volatile metabolites, comprising 51 terpenic compounds, 45 organosulfur compounds, 31 aldehydes, 37 esters, 29 ketones, 28 alcohols, 23 furanic compounds, 22 hydrocarbons, 19 benzene compounds, 13 nitrogenous compounds, 9 carboxylic acids, 7 ethers, 4 halogenated compounds and 3 naphthalene derivatives, were positively identified. Each investigated fruit and vegetable showed a specific volatile metabolomic profile. The obtained results revealed that terpenic compounds, to which are associated antimicrobial, antioxidant, and anticancer activities, are the most predominant chemical family in beetroot (61%), orange carrot (58%) and white carrot (61%), while organosulfur compounds (antiviral activity) are dominant in onion, garlic and watercress. Broccoli and spinach are essentially constituted by alcohols and aldehydes (enzyme-inhibition and antimicrobial properties), while fruits from the Solanaceae family are characterized by esters in tamarillo and aldehydes in tomato.

The synthetic cannabinoids phenomenon: from structure to toxicological properties. A review.

The word "cannabinoid" refers to every chemical substance, regardless of structure or origin, that joins the cannabinoid receptors of the body and brain and that have similar effects to those produced by the Cannabis plant and based on their source of production, cannabinoids can be classified into endocannabinoids, phytocannabinoids and synthetic cannabinoids. Synthetic cannabinoids represent the largest class of drugs detected through the EU Early Warning System with a total of 190 substances notified from 2008 to 2018 and about 280 have been reported worldwide to the United Nations Office on Drugs and Crime. Sprayed on natural herb mixtures with the aim to mimic the euphoria effect of cannabis and sold as "herbal smoking blends" or "herbal incense" under brand names like "Spice" or "K2", synthetic cannabinoids are available from websites for the combination with herbal materials or more recently, for the use in e-cigarettes. Currently labeled as "not for human consumption" to circumvent legislation, their legal status varies by country with many government institutions currently pushing for their control. However, due to the emergence of new substances, it requires a constant update of the list of controlled drugs. Little is known about how these substances work and their toxic effects in humans and the same product could vary not only in the amount and in the type of substance added. In the last years, synthetic cannabinoids have been associated with deaths and acute intoxications in Europe and, despite a range of new measures introduced in this area, continue to represent a challenge to current drug policy models. These synthetic substances are much more potent than natural cannabis, as well as displayed greater efficacy, acting as full agonists at the cannabinoid receptors. It is possible that, along with being highly potent, some may also have long half-lives, potentially leading to a prolonged psychoactive effect. The present work provides a review on existing literature about the development of synthetic cannabinoids as substances of abuse, current patterns of abuse and their legal status, chemical classification, and some pharmacological and toxicological properties.

Synthetic cathinones: an evolving class of new psychoactive substances.

Synthetic cathinones (SCat) are amphetamine-like psychostimulants that emerged onto drug markets as "legal" alternatives to illicit drugs such as ecstasy, cocaine, and amphetamines. Usually they are sold as "bath salts," "plant food," or "research chemicals," and rapidly gained popularity amongst drugs users due to their potency, low cost, and availability. In addition, internet drug sales have been replacing the old way of supplying drugs of abuse, contributing to their rapid spread. Despite the legislative efforts to control SCat, new derivatives continue to emerge on the recreational drugs market and their abuse still represents a serious public health issue. To date, about 150 SCat have been identified on the clandestine drugs market, which are one of the largest groups of new psychoactive substances (NPS) monitored by the United Nations Office on Drugs and Crime and the European Monitoring Center for Drugs and Drug Addiction. Similar to the classical stimulants, SCat affect the levels of catecholamines in the central nervous system, which results in their psychological, behavioral and toxic effects. Generally, the effects of SCat greatly differ from drug to drug and relatively little information is available about their pharmacology. The present work provides a review on the development of SCat as substances of abuse, current patterns of abuse and their legal status, chemical classification, known mechanisms of action, and their toxicological effects.

Current trends on microextraction by packed sorbent - fundamentals, application fields, innovative improvements and future applications.

MEPS, the acronym of microextraction by packed sorbent, is a simple, fast and user- and environmentally-friendly miniaturization of the popular solid-phase extraction technique (SPE). In fact, it has been widely shown that MEPS can easily replace SPE for most, if not all, previous applications. It can attain this with obvious gains in sample and solvent usage, which is greatly reduced without compromising the extraction efficiency. Furthermore, MEPS can be operated with semiautomatic electronic syringes, making it very reliable and versatile, particularly to handle very low and very high sample volumes. This review will focus on the strengths and weaknesses of this technique and the different MEPS architectures commercially available in the context of the MEPS applications reported in the last five years. Additionally, innovative improvements will be highlighted, particularly those related with new applications and recent MEPS configurations and sorbents, such as the controlled directional flow or the innovative µSPEed variant.

Repeated Mesenchymal Stromal Cell Treatment Sustainably Alleviates Machado-Joseph Disease.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3, the most common dominant spinocerebellar ataxia (SCA) worldwide, is caused by over-repetition of a CAG repeat in the ATXN3/MJD1 gene, which translates into a polyglutamine tract within the ataxin-3 protein. There is no treatment for this fatal disorder. Despite evidence of the safety and efficacy of mesenchymal stromal cells (MSCs) in delaying SCA disease progression in exploratory clinical trials, unanticipated regression of patients to the status prior to treatment makes the investigation of causes and solutions urgent and imperative. In the present study, we compared the efficacy of a single intracranial injection with repeated systemic MSC administration in alleviating the MJD phenotype of two strongly severe genetic rodent models. We found that a single MSC transplantation only produces transient effects, whereas periodic administration promotes sustained motor behavior and neuropathology alleviation, suggesting that MSC therapies should be re-designed to get sustained beneficial results in clinical practice. Furthermore, MSC promoted neuroprotection, increased the levels of GABA and glutamate, and decreased the levels of Myo-inositol, which correlated with motor improvements, indicating that these metabolites may serve as valid neurospectroscopic biomarkers of disease and treatment. This study makes important contributions to the design of new clinical approaches for MJD and other SCAs/polyglutamine disorders.

The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients.

Type 1 diabetes in children is not a predisposing factor for oral yeast colonization.

Type 1 diabetes mellitus (T1D) is considered a risk factor associated with oral yeast infections. The aim of this study was to evaluate the yeast oral carriage (in saliva and mucosal surface) of children with T1D and potential relation with host factors, particularly the subset of CD4+ T cells. Yeasts were quantified and identified in stimulated saliva and in cheek mucosal swabs of 133 diabetic T1D and 72 healthy control subjects. Salivary lymphocytes were quantified using flow cytometry. The presence of yeasts in the oral cavity (60% of total patients) was not affected by diabetes, metabolic control, duration of the disease, salivary flow rate or saliva buffer capacity, by age, sex, place of residence, number of daily meals, consumption of sweets or frequency of tooth brushing. Candida albicans was the most prevalent yeast species, but a higher number of yeast species was isolated in nondiabetics. T1D children with HbA1c ≤ 7.5 (metabolically controlled) presented higher number of CD4+ T salivary subsets when compared with the other groups of children (non-diabetic and nonmetabolically controlled) and also presented the highest number of individuals without oral yeast colonization. In conclusion, T1D does not predisposes for increased oral yeast colonization and a higher number of salivary CD4+T cells seems to result in the absence of oral colonization by yeasts.

Natural killer cell-based adoptive immunotherapy eradicates and drives differentiation of chemoresistant bladder cancer stem-like cells.

BACKGROUND: High-grade non-muscle invasive bladder cancer (NMIBC) has a high risk of recurrence and progression to muscle-invasive forms, which seems to be largely related to the presence of tumorigenic stem-like cell populations that are refractory to conventional therapies. Here, we evaluated the therapeutic potential of Natural Killer (NK) cell-based adoptive immunotherapy against chemoresistant bladder cancer stem-like cells (CSCs) in a pre-clinical relevant model, using NK cells from healthy donors and NMIBC patients. METHODS: Cytokine-activated NK cells from healthy donors and from high-grade NMIBC patients were phenotypically characterized and assayed in vitro against stem-like and bulk differentiated bladder cancer cells. Stem-like cells were isolated from two bladder cancer cell lines using the sphere-forming assay. The in vivo therapeutic efficacy was evaluated in mice bearing a CSC-induced orthotopic bladder cancer. Animals were treated by intravesical instillation of interleukin-activated NK cells. Tumor response was evaluated longitudinally by non-invasive bioluminescence imaging. RESULTS: NK cells from healthy donors upon activation with IL-2 and IL-15 kills indiscriminately both stem-like and differentiated tumor cells via stress ligand recognition. In addition to cell killing, NK cells shifted CSCs towards a more differentiated phenotype, rendering them more susceptible to cisplatin, highlighting the benefits of a possible combined therapy. On the contrary, NK cells from NMIBC patients displayed a low density on NK cytotoxicity receptors, adhesion molecules and a more immature phenotype, losing their ability to kill and drive differentiation of CSCs. The local administration, via the transurethral route, of activated NK cells from healthy donors provides an efficient tumor infiltration and a subsequent robust tumoricidal activity against bladder cancer with high selective cytolytic activity against CSCs, leading to a dramatic reduction in tumor burden from 80 % to complete remission. CONCLUSION: Although pre-clinical, our results strongly suggest that an immunotherapeutic strategy using allogeneic activated NK cells from healthy donors is effective and should be exploited as a complementary therapeutic strategy in high-risk NMIBC patients to prevent tumor recurrence and progression.

Does progesterone administration in preterm labor influence Treg cells?

OBJECTIVES: The aim of this study was to determine if the actions of progesterone on preterm labor are accomplished through modulation of the percentage of regulatory T-cells (Treg). METHODS: The study was a cohort pilot study made in a single center tertiary obstetrical unit with women in preterm labor arrested with tocolytic treatment. Variation of the number and percentage of Treg cells obtained from peripheral blood samples of women with preterm labor were calculated by flow cytometry, before and after progesterone administration. RESULTS: In the paired samples for each patient, there was a significant difference in the Treg cell pool after progesterone treatment, with an increase in both their percentage (48.9 vs. 53; P=0.07) and absolute number (14.8 vs. 56.5 cells/µL; P=0.046). CONCLUSIONS: This research demonstrated a considerable increase in the Treg cell pool after progesterone treatment. This indicates a possible mechanism for progesterone treatment benefits in preterm labor, potentially increasing its more rational use.

A gene in the multidrug and toxic compound extrusion (MATE) family confers aluminum tolerance in sorghum.

Crop yields are significantly reduced by aluminum toxicity on highly acidic soils, which comprise up to 50% of the world's arable land. Candidate aluminum tolerance proteins include organic acid efflux transporters, with the organic acids forming non-toxic complexes with rhizosphere aluminum. In this study, we used positional cloning to identify the gene encoding a member of the multidrug and toxic compound extrusion (MATE) family, an aluminum-activated citrate transporter, as responsible for the major sorghum (Sorghum bicolor) aluminum tolerance locus, Alt(SB). Polymorphisms in regulatory regions of Alt(SB) are likely to contribute to large allelic effects, acting to increase Alt(SB) expression in the root apex of tolerant genotypes. Furthermore, aluminum-inducible Alt(SB) expression is associated with induction of aluminum tolerance via enhanced root citrate exudation. These findings will allow us to identify superior Alt(SB) haplotypes that can be incorporated via molecular breeding and biotechnology into acid soil breeding programs, thus helping to increase crop yields in developing countries where acidic soils predominate.

Incomplete transfer of accessory loci influencing SbMATE expression underlies genetic background effects for aluminum tolerance in sorghum.

Impaired root development caused by aluminum (Al) toxicity is a major cause of grain yield reduction in crops cultivated on acid soils, which are widespread worldwide. In sorghum, the major Al-tolerance locus, AltSB , is due to the function of SbMATE, which is an Al-activated root citrate transporter. Here we performed a molecular and physiological characterization of various AltSB donors and near-isogenic lines harboring various AltSB alleles. We observed a partial transfer of Al tolerance from the parents to the near-isogenic lines that was consistent across donor alleles, emphasizing the occurrence of strong genetic background effects related to AltSB . This reduction in tolerance was variable, with a 20% reduction being observed when highly Al-tolerant lines were the AltSB donors, and a reduction as great as 70% when other AltSB alleles were introgressed. This reduction in Al tolerance was closely correlated with a reduction in SbMATE expression in near-isogenic lines, suggesting incomplete transfer of loci acting in trans on SbMATE. Nevertheless, AltSB alleles from the highly Al-tolerant sources SC283 and SC566 were found to retain high SbMATE expression, presumably via elements present within or near the AltSB locus, resulting in significant transfer of the Al-tolerance phenotype to the derived near-isogenic lines. Allelic effects could not be explained by coding region polymorphisms, although occasional mutations may affect Al tolerance. Finally, we report on the extensive occurrence of alternative splicing for SbMATE, which may be an important component regulating SbMATE expression in sorghum by means of the nonsense-mediated RNA decay pathway.

Genetic dissection of Al tolerance QTLs in the maize genome by high density SNP scan.

BACKGROUND: Aluminum (Al) toxicity is an important limitation to food security in tropical and subtropical regions. High Al saturation on acid soils limits root development, reducing water and nutrient uptake. In addition to naturally occurring acid soils, agricultural practices may decrease soil pH, leading to yield losses due to Al toxicity. Elucidating the genetic and molecular mechanisms underlying maize Al tolerance is expected to accelerate the development of Al-tolerant cultivars. RESULTS: Five genomic regions were significantly associated with Al tolerance, using 54,455 SNP markers in a recombinant inbred line population derived from Cateto Al237. Candidate genes co-localized with Al tolerance QTLs were further investigated. Near-isogenic lines (NILs) developed for ZmMATE2 were as Al-sensitive as the recurrent line, indicating that this candidate gene was not responsible for the Al tolerance QTL on chromosome 5, qALT5. However, ZmNrat1, a maize homolog to OsNrat1, which encodes an Al(3+) specific transporter previously implicated in rice Al tolerance, was mapped at ~40 Mbp from qALT5. We demonstrate for the first time that ZmNrat1 is preferentially expressed in maize root tips and is up-regulated by Al, similarly to OsNrat1 in rice, suggesting a role of this gene in maize Al tolerance. The strongest-effect QTL was mapped on chromosome 6 (qALT6), within a 0.5 Mbp region where three copies of the Al tolerance gene, ZmMATE1, were found in tandem configuration. qALT6 was shown to increase Al tolerance in maize; the qALT6-NILs carrying three copies of ZmMATE1 exhibited a two-fold increase in Al tolerance, and higher expression of ZmMATE1 compared to the Al sensitive recurrent parent. Interestingly, a new source of Al tolerance via ZmMATE1 was identified in a Brazilian elite line that showed high expression of ZmMATE1 but carries a single copy of ZmMATE1. CONCLUSIONS: High ZmMATE1 expression, controlled either by three copies of the target gene or by an unknown molecular mechanism, is responsible for Al tolerance mediated by qALT6. As Al tolerant alleles at qALT6 are rare in maize, marker-assisted introgression of this QTL is an important strategy to improve maize adaptation to acid soils worldwide.

Re-exploring the high-throughput potential of microextraction techniques, SPME and MEPS, as powerful strategies for medical diagnostic purposes. Innovative approaches, recent applications and future trends.

The human population continues to grow exponentially in the fast developing and most populated countries, whereas in Western Europe it is getting older and older each year. This inevitably raises the demand for better and more efficient medical services without increasing the economic burden in the same proportion. To meet these requirements, improvement of medical diagnosis is certainly a key aspect to consider. Therefore, we need powerful analytical methodologies able to go deeper and further in the characterization of human metabolism and identification of disease biomarkers and endogenous molecules in body fluids and tissues. The ultimate goal is to have a reliable and early medical diagnosis, mitigating the disease complications as much as possible. Microextraction techniques (METs) represent a key step in these analytical methodologies by providing samples in the suitable volumes and purification levels necessary for the characterization of the target analytes. In this aspect, solid-phase microextraction (SPME) and, more recently, microextraction by packed sorbent (MEPS), are powerful sample preparation techniques, characterized by their reduced time of analysis, low solvent consumption, and broad application. Moreover, as miniaturized techniques, they can be easily automatized to have a high-throughput performance in the clinical environment. In this review, we explore some of the most interesting MEPS and SPME applications, focusing on recent trends and applications to medical diagnostic, particularly the in vivo and near real time applications.

Effectiveness of global postural reeducation compared to segmental exercises on function, pain, and quality of life of patients with scapular dyskinesis associated with neck pain: a preliminary clinical trial.

OBJECTIVE: The purpose of this study was to assess the effectiveness of global postural reeducation (GPR) relative to segmental exercises (SE) in the treatment of scapular dyskinesis (SD) associated with neck pain. METHODS: Participants with SD and neck pain (n = 30) aged 18 to 65 years were randomly assigned to one of two groups: GPR and SE (stretching exercises). The upper extremity was assessed using the Disabilities of the Arm, Shoulder, and Hand questionnaire; function of the neck was estimated using the Neck Disability Index; pain severity was measured using a visual analogical scale; and health-related quality of life was assessed using the Short Form-12. Assessments were conducted at baseline and after 10 weekly sessions (60 minutes each). The significance level adopted was α < .05. RESULTS: For pre-post treatment comparisons, GPR was significantly associated with improvements in function of neck and upper extremities, pain, and physical and mental domains of quality of life (P < .05). Segmental exercises improved function of upper extremities and of the neck and severity of pain (P < .05). When contrasting groups, GPR was significantly superior to SE in improving pain and physical domains of the quality of life. CONCLUSION: This study showed that GPR and SE had similar effects on function of the neck and upper extremity in patients with SD associated with neck pain. When comparing groups, GPR was superior to SE in improving pain and quality of life.

FUNCTIONAL CAPACITY IN PATIENTS WITH KNEE OSTEOARTHRITIS: CROSS-SECTIONAL STUDY.

Knee osteoarthritis (KOA) is a disabling inflammatory disease that makes walking and activities of daily living difficult. This condition can reduce functional capacity and increase the risk for surgery. OBJECTIVE: To know the functional capacity of patients with KOA evaluated by the six-minute walk test (6MWT). METHOD: This cross-sectional study evaluated age, gender, weight, BMI, pain (VAS 90-100), physical disability (WOMAC 0-96), degree of joint damage by radiographic imaging, and 6MWT. RESULTS: A total of 176 patients referred by Orthopedics were evaluated, with the inclusion of 164 participants. The mean age was 61.89 ± 10.62 years, 81% women, 67% with cardiovascular disease, hypertension and/or diabetes, 81% obese, with moderate pain (VAS 47.74 ± 29.27) and according to WOMAC, most had severe or very severe disability. The distance covered in the 6MWT was 354.03 ± 102.03m, 67% of the predicted distance. The maximum heart rate achieved was 107.27 ± 17.71 bpm, which characterizes 68% of the predicted by age. Only 12% of the sample showed a marked drop in oxygenation in the 6MWT and 40% had a recovery heart rate in the 1st minute below 15 bpm. CONCLUSION: Patients with KOA, who were evaluated by the 6MWT, have low functional capacity and physical deconditioning. Level of Clinical Evidence III, Case Control Study.

A osteoartrite de joelho (OAJ) é uma doença inflamatória incapacitante que dificulta as atividades de vida diária do indivíduo. Esta condição pode reduzir a capacidade funcional e aumentar o risco de cirurgia, caso necessária. Objetivo: Conhecer a capacidade funcional de pacientes com OAJ, avaliada pelo teste de caminhada de seis minutos (TC6M). Métodos: Neste estudo transversal, avaliamos idade, sexo, peso, índice de massa corporal (IMC), dor (escala visual analógica ­ EVA 90-100), incapacidade física (Western Ontario and McMaster Universities Osteoarthritis Index ­ WOMAC 0-96), grau de lesão articular por imagem radiográfica e TC6M. Resultados: Foram avaliados 176 pacientes encaminhados pela Ortopedia, com a inclusão de 164 participantes. Na amostra, verificou-se: média de idade de 61,89 ± 10,62 anos; 81% de mulheres; 67% com doença cardiovascular, hipertensão e/ou diabetes; 81% de obesos; com dor moderada (EVA 47,74 ± 29,27); e, segundo WOMAC, maioria com incapacidade intensa ou muito intensa. A distância percorrida no TC6M foi 354,03 ± 102,03 m, sendo esse valor 67% da distância prevista. A frequência cardíaca máxima alcançada foi de 107,27 ± 17,71 bpm, que caracteriza 68% da prevista pela idade. Somente 12% apresentaram acentuada queda de oxigenação no TC6M e 40% apresentaram frequência cardíaca de recuperação no primeiro minuto inferior a 15 bpm. Conclusão: Os pacientes com OAJ, que foram avaliados pelo TC6M, apresentaram baixa capacidade funcional e descondicionamento físico. Nível de Evidência III, Estudo de Caso Controle.

Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells.

Periodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compared to PDT, T2D patients, and control individuals. PBMCs were analyzed for mitochondrial respiration, reactive oxygen species, antioxidant proteins, and expression of Nrf2-target genes. PDT and T2D-PDT patients exhibited altered periodontal clinical markers, while T2D and T2D-PDT patients displayed increased blood HbA1c. Decreased oxygen consumption and ATP production were observed in the PDT patient's PBMCs. PDT and T2D-PDT PBMCs also evidenced increased H2O2 levels and reduced catalase levels (also detected in T2D patients), whereas a compromised glutathione cycle was observed in T2D-PDT patients. PBMCs from both T2D or T2D-PDT patients showed increased Nrf2 protein levels, enhanced GCL activity and GCL-catalytic subunit protein levels, and maintained GCLc, GST, and HO-1 mRNA levels. In contrast, the expressions of Nrf2-target genes were significantly diminished in the PDT patient's PBMCs. Decreased SOD1 and GST mRNA levels were also observed in CD3+CD8+-lymphocytes derived from PDT and T2D-PDT patients. In conclusion, PBMCs from T2D-PDT patients showed major redox changes, while mononuclear cells from PDT patients showed mitochondrial deregulation and reduced expression of Nrf2-target genes.

EXERCISES AND NEUROMUSCULAR ELECTRIC STIMULATION FOR MEDIAL LONGITUDINAL ARCH: CLINICAL TRIAL.

Objective: The extrinsic muscles, such as the posterior tibialis and long flexor of the hallux and the intrinsic of the foot, are part of the active subsystem of the central system of the foot and play an essential role in the control of the medial longitudinal arch resulting from difficulty in contracting the muscle, neuromuscular electrostimulation (NMES) becomes a resource combined with strengthening and recommended for rehabilitation. T this work aims to evaluate the effectiveness of NMES associated with exercise in deforming the medial longitudinal arch. Methods: This is a randomized blind clinical trial. 60 asymptomatic participants were divided into three groups: NMES, exercise and control. The NMES and exercise group performed seven exercises for the intrinsic and extrinsic muscles twice a week for 6 weeks, and the NMES group used an NMES associated with five exercises. Navicular height and medial longitudinal arch angle were taken before and after the intervention period. Results: No statistically significant differences existed between groups for navicular height and medial longitudinal arch angle. Conclusion: NMES associated with exercise does not change the characteristics of the medial longitudinal arch in association with asymptomatic. Level of Evidence I; Randomized clinical trial.

Objetivo: Os músculos extrínsecos, como o tibial posterior e flexor longo do hálux e os intrínsecos do pé fazem parte do subsistema ativo do foot core system e exercem papel essencial no controle do arco longitudinal medial. Devido à dificuldade na contração desses músculos, a eletroestimulação neuromuscular (EENM) torna-se um recurso aliado ao fortalecimento e é recomendada para reabilitação. O objetivo desse trabalho é avaliar a eficácia da EENM associada ao exercício na deformação do arco longitudinal medial. Métodos: Este é um ensaio clínico randomizado cego. 60 participantes assintomáticos foram divididos em três grupos: EENM, exercício e controle. O grupo EENM e exercício realizaram sete exercícios para os músculos intrínsecos e extrínsecos duas vezes por semana por seis semanas, sendo o grupo EENM utilizou a EENM associada a cinco exercícios. A altura do navicular e o ângulo do arco longitudinal medial foram medidos antes e após o período de intervenção. Resultados: Não houve diferenças estatisticamente significativas entre os grupos para a altura do navicular e ângulo do arco longitudinal medial. Conclusão: A EENM associada ao exercício não altera as características do arco longitudinal medial em indivíduos assintomáticos. Nível de Evidência I; Estudo Clínico Randomizado.