Transcranial photobiomodulation increases cognition and serum BDNF levels in adults over 50 years: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: There is a significant lack of therapeutic options for mild cognitive impairment (MCI), which is rapidly becoming a global epidemic due to aging. Transcranial photobiomodulation (t-PBM) involves delivering near-infrared light (NIR) to the scalp, targeting cortical areas of the brain. NIR t-PBM has recently emerged as a potential therapy for various neurodegenerative conditions, including memory issues. AIMS: This study aimed to evaluate cognition scores (primary outcome), depression, anxiety, resilience scores, neuroplasticity, and neurodegeneration biomarkers (secondary outcomes) in individuals with MCI undergoing t-PBM therapy or receiving a placebo. MATERIALS AND METHODS: A total of 93 older adult individuals with MCI were randomly assigned to either a t-PBM (n = 47) or Placebo (n = 46) group. Clinical assessments were conducted at baseline, 60 days post-treatment, and a 150-day follow-up. We also measured serum levels of brain-derived neurotrophic factor (BDNF), a neuroplasticity biomarker, as well as neuron-specific enolase (NSE) and calcium-binding protein B (S100B), which are neurodegeneration biomarkers. Intervention effects were analyzed using repeated measures (RM) two-way ANOVA followed by Tukey post hoc test. Fischer's exact test and Generalized Estimating Equations (GEE) were also applied. RESULTS: Of the 93 older adults individuals invited to participate, 76 (t-PBM: 40, placebo: 36) completed the study. The t-PBM significantly improved cognition as measured by the Montreal Cognitive Assessment (MoCA) compared to placebo (p = 0.0301). The delta values for MoCA scores were 3.20 in the t-PBM group and 1.97 in the placebo group. This effect persisted until the three-month follow-up, accompanied by increased BDNF levels in the t-PBM group but not in the placebo group (p = 0.0046). The delta values for BDNF were 821.94 in the t-PBM group and 359.41 in the placebo group. t-PBM did not alter depression, anxiety, resilience scores, nor the levels of NSE and S100B in individuals with MCI. CONCLUSION: The t-PBM increases cognitive function and BDNF levels in adults with MCI. Its application as an adjunctive treatment may play a crucial role in preventing neurodegenerative diseases.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats.

Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of the reduction of interleukin-6 levels. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Accuracy of neck circumference in the diagnosis of overweight in children.

OBJECTIVE: The objective of this study was to estimate the accuracy of measuring neck circumference as a diagnostic method for overweight in 10-year-old children. METHODS: A cross-sectional diagnostic accuracy study was performed in 2019. The population was composed of 942 school children from the municipality of Palhoça, SC, Brazil. For each measurement of the neck circumference, sensitivity, specificity, positive and negative predictive values, likelihood ratio for a positive test, and accuracy were estimated using the receiver operator characteristic curve, with body mass index as a reference. RESULTS: The estimated overall accuracy was 88.9%. For males, the accuracy was 90.1%, and for females, 88.5%. A 30.0 cm neck circumference had a sensitivity of 22.8%, a specificity of 95.4%, a positive predictive value of 76.6%, a negative predictive value of 65.3%, a likelihood ratio for a positive test of 5.0, and an accuracy of 66.7% for all students. CONCLUSION: Neck circumference showed a global accuracy of 88.9% as a method for diagnosing overweight in 10-year-old children. Predictive values showed high values, mainly starting with a neck circumference of 30 cm.

Amelioration of Neurochemical Alteration and Memory and Depressive Behavior in Sepsis by Allopurinol, a Tryptophan 2,3-Dioxygenase Inhibitor.

BACKGROUND: In response to inflammation and other stressors, tryptophan is catalyzed by Tryptophan 2,3-Dioxygenase (TDO), which leads to activation of the kynurenine pathway. Sepsis is a serious condition in which the body responds improperly to an infection, and the brain is the inflammation target in this condition. OBJECTIVE: This study aimed to determine if the induction of TDO contributes to the permeability of the Blood-Brain Barrier (BBB), mortality, neuroinflammation, oxidative stress, and mitochondrial dysfunction, besides long-term behavioral alterations in a preclinical model of sepsis. METHODS: Male Wistar rats with two months of age were submitted to the sepsis model using Cecal Ligation and Perforation (CLP). The rats received allopurinol (Allo, 20 mg/kg, gavage), a TDO inhibitor, or a vehicle once a day for seven days. RESULTS: Sepsis induction increased BBB permeability, IL-6 level, neutrophil infiltrate, nitric oxide formation, and oxidative stress, resulting in energy impairment in 24h after CLP and Allo administration restored these parameters. Regarding memory, Allo restored short-term memory impairment and decreased depressive behavior. However, no change in survival rate was verified. CONCLUSION: In summary, TDO inhibition effectively prevented depressive behavior and memory impairment 10 days after CLP by reducing acute BBB permeability, neuroinflammation, oxidative stress, and mitochondrial alteration.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats / A estimulação elétrica previne a atrofia muscular e a diminuição da interleucina-6 em músculos paralisados após lesão da medula espinal em ratos

Abstract Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of interleukin-6 level reduction. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Resumo Objetivo Analisar o trofismo muscular e a de interleucina-6 no músculo bíceps braquial de ratas com lesão medular cervical incompleta tratados com estimulação elétrica neuromuscular (EENM). Métodos Ratas adultas foram submetidas à hemissecção da medula espinal em C5-C7 e a um protocolo de EENM de 5 semanas. O trofismo do bíceps braquial foi avaliado pela relação peso muscular/peso corporal e análise histológica. A expressão de interleucina-6 no bíceps braquial foi medida usando ensaio de imunoabsorção enzimática. Resultados O grupo tratado com EENM apresentou preservação do trofismo muscular, assim como prevenção da redução dos níveis de interleucina-6. Conclusão A lesão da medula espinal causa atrofia muscular e diminui a expressão de interleucina-6. Essas alterações são parcialmente prevenidas pela EENM. Os resultados sugerem um possível mecanismo de ação da EENM e ressaltam o uso clínico desta ferramenta terapêutica.

Accuracy of neck circumference in the diagnosis of overweight in children

SUMMARY OBJECTIVE: The objective of this study was to estimate the accuracy of measuring neck circumference as a diagnostic method for overweight in 10-year-old children. METHODS: A cross-sectional diagnostic accuracy study was performed in 2019. The population was composed of 942 school children from the municipality of Palhoça, SC, Brazil. For each measurement of the neck circumference, sensitivity, specificity, positive and negative predictive values, likelihood ratio for a positive test, and accuracy were estimated using the receiver operator characteristic curve, with body mass index as a reference. RESULTS: The estimated overall accuracy was 88.9%. For males, the accuracy was 90.1%, and for females, 88.5%. A 30.0 cm neck circumference had a sensitivity of 22.8%, a specificity of 95.4%, a positive predictive value of 76.6%, a negative predictive value of 65.3%, a likelihood ratio for a positive test of 5.0, and an accuracy of 66.7% for all students. CONCLUSION: Neck circumference showed a global accuracy of 88.9% as a method for diagnosing overweight in 10-year-old children. Predictive values showed high values, mainly starting with a neck circumference of 30 cm.

Effects of auriculotherapy on anxiety and biomarkers in Primary Health Care: a clinical trial.

OBJECTIVE: to assess the effects of auriculotherapy on anxiety and brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) serum levels in adults assisted in Primary Health Care. METHODS: a pre-experimental pilot clinical trial. Information was obtained from 19 patients using the State-Trait Anxiety Inventory (STAI) and analysis of BDNF, NSE and S100B serum levels. RESULTS: the pre-intervention anxiety score in the IDATE-Trait was 52.11±6.691 (CV 12.84%) and the assessment after auriculotherapy was significantly lower (43.72±8.141; CV 18.62%; P=0.0007). S100B levels were significantly reduced after auriculotherapy (from 64.03±72.18 to 54.03±68.53 pg/mL; CV 126.8%; P=0.0023). CONCLUSION: auriculotherapy effectively reduced anxiety levels. It proved to be safe and easy to apply, allowing nurses to perform this technique autonomously. A reduction of S100B was also evidenced, demonstrating possible prevention of neuronal damage.

Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation.

Objective: This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation. Methods: The pain model was induced by intraplantar (i.pl.) injection of Freund's complete adjuvant (CFA). Sixty-four male Swiss mice (35-40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days. Results: pVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord. Conclusion: pVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain.

Peripheral Activation of Formyl Peptide Receptor 2/ALX by Electroacupuncture Alleviates Inflammatory Pain by Increasing Interleukin-10 Levels and Catalase Activity in Mice.

In the context of the electroacupuncture (EA) neurobiological mechanisms, we have previously demonstrated the involvement of formyl peptide receptor 2 (FPR2/ALX) in the antihyperalgesic effect of EA. The present study investigated the involvement of peripheral FPR2/ALX in the antihyperalgesic effect of EA on inflammatory cytokines levels, oxidative stress markers and antioxidant enzymes in an animal model of persistent inflammatory pain. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2/10 Hz, ST36-SP6, 20 minutes) for 4 consecutive days. From the first to the fourth day after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or saline before EA. Levels of inflammatory cytokines (TNF, IL-6, IL-4 and IL-10), antioxidant enzymes (catalase and superoxide dismutase), oxidative stress markers (TBARS, protein carbonyl, nitrite/nitrate ratio), and myeloperoxidase activity were measured in paw tissue samples. As previously demonstrated, i.pl. injection of the FPR2/ALX antagonist prevented the antihyperalgesic effect induced by EA. Furthermore, animals treated with EA showed higher levels of IL-10 and catalase activity in the inflamed paw, and these effects were prevented by the antagonist WRW4. EA did not change levels of TNF and IL-6, SOD and MPO activity, and oxidative stress markers. Our work demonstrates that the antihyperalgesic effect of EA on CFA-induced inflammatory pain could be partially associated with higher IL-10 levels and catalase activity, and that these effects may be dependent, at least in part, on the activation of peripheral FPR2/ALX.

Animal models of complex regional pain syndrome: A scoping review.

BACKGROUND: complex regional pain syndrome (CRPS) leads to a debilitating chronic pain condition. The lack of cause, etiology, and treatment for CRPS has been widely explored in animal models. OBJECTIVE: Provide a comprehensive framework of the animal models used for investigating CRPS. ELIGIBILITY CRITERIA: Preclinical studies to induce the characteristics of CRPS, with a control group, in any language or publication date. SOURCES OF EVIDENCE: The search was performed in the Medline (PubMed) and ScienceDirect databases. RESULTS: 93 studies are included. The main objective of the included studies was to understand the CRPS model. Rats, males and adults, exposed to ischemia/reperfusion of the paw or fracture of the tibia were the most common characteristics. Nociceptive evaluation using von Frey monofilaments was the most widely adopted in the studies. CONCLUSIONS: For the best translational science between the animal models and individuals with CRPS, future studies should include more heterogeneous animals, and multiple assessment tools, in addition to improving the description and performance of measures that reduce the risk of bias.

Electrical Stimulation of the Auricular Branch Vagus Nerve Using Random and Alternating Frequencies Triggers a Rapid Onset and Pronounced Antihyperalgesia via Peripheral Annexin A1-Formyl Peptide Receptor 2/ALX Pathway in a Mouse Model of Persistent Inflammatory Pain.

This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) by comparing the effects of alternating and random frequencies in an animal model of persistent inflammatory hyperalgesia. The model was induced by Freund's complete adjuvant (CFA) intraplantar (i.pl.) injection. Mice were treated with different protocols of time (10, 20, or 30 min), ear laterality (right, left or both), and frequency (alternating or random). Mechanical hyperalgesia was evaluated, and some groups received i.pl. WRW4 (FPR2/ALX antagonist) to determine the involvement. Edema, paw surface temperature, and spontaneous locomotor activity were evaluated. Interleukin-1ß, IL-6, IL-10, and IL4 levels were verified by enzyme-linked immunosorbent assay. AnxA1, FPR2/ALX, neutrophil, M1 and M2 phenotype macrophage, and apoptotic cells markers were identified using western blotting. The antihyperalgesic effect pVNS with alternating and random frequency effect is depending on the type of frequency, time, and ear treated. The pVNS random frequency in the left ear for 10 min had a longer lasting antihyperalgesic effect, superior to classical stimulation using alternating frequency and the FPR2/ALX receptor was involved in this effect. There was a reduction in the levels of pro-inflammatory cytokines and an increase in the immunocontent of AnxA1 and CD86 in mice paw. pVNS with a random frequency in the left ear for 10 min showed to be optimal for inducing an antihyperalgesic effect. Thus, the random frequency was more effective than the alternating frequency. Therefore, pVNS may be an important adjunctive treatment for persistent inflammatory pain.

Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study.

Background: Obesity is one of the major public health problems worldwide and contributes to the onset of many diseases, especially the ones related to the metabolic syndrome. The new Dietary Guidelines for the Brazilian population bring a new food classification based on food processing and prioritizes the consumption of fresh or minimally processed foods. Aim: This study analyzed the effects of an educational intervention on obese women, on their weight loss, quality of life, components of the metabolic syndrome and pain. Methods: Randomized controlled pilot study, including 40 obese women, randomized into 2 groups: control group and intervention group. An educational intervention with 5 biweekly meetings of 90 min based on the Dietary Guidelines for the Brazilian population (2014) was carried out involving the intervention group. Parameters related to weight loss, quality of life (SF-36), pain (McGill), bioelectrical impedance analysis, cardiorespiratory fitness, and serum and clinical components of metabolic syndrome, as well as serum concentrations of cytokines were assessed. Results: Significantly decrease of body mass, waist and hip circumferences, basal metabolic rate, extracellular water, body capacitance, and body cell mass were observed in the intervention group after 3 months. Reduction of pain and improvement in quality of life and cardiorespiratory fitness were also observed in the intervention group. There were reductions in waist circumference and glycemia, components of metabolic syndrome. Conclusions: This study showed that the educational intervention can be associated with weight loss, increase in quality of life, reduction of pain, and better metabolic syndrome parameters in obese women.

Maternal immune activation induces autism-like behavior and reduces brain-derived neurotrophic factor levels in the hippocampus and offspring cortex of C57BL/6 mice.

Prenatal factors such as viral or bacterial infections occurring mainly during the first trimesters of pregnancy can increase the incidence of autism spectrum disorder (ASD) in children. In an animal model, it is already known that maternal immune activation (MIA) induces autistic-like behavior. However, it is unclear whether this behavior presents itself in young animals. In this preclinical experimental study, we investigated in the offspring of C57BL/6 female mice submitted to MIA with lipopolysaccharide (LPS), typically altered behaviors in ASD, such as social interaction and stereotyped self-grooming movement, as well as the levels of the brain-derived neurotrophic factor (BDNF) and interleukin 17A (IL-17A) in the hippocampus and cortex, at 28 and 60 days. Adult animals aged 60 days, offspring of females submitted to MIA, showed a decrease in the time of social interaction and an increase in the number of self-cleaning movements. In the hippocampus of the offspring of females submitted to MIA, a decrease in BDNF levels was found at 28 days and 60 days of life, and a decrease in IL-17A levels only at 60 days. The levels of BDNF and IL-17A did not change in the cortex of the offspring of mice submitted to MIA at the evaluated times. Young animals aged 28 days still showed typical behavior, without social deficits and stereotyped movements that characterize ASD, which suggests that at this age it is still not possible to observe the repercussions of MIA in this model. In the neurochemical issues of the hippocampal region, impairment of BDNF levels has already been demonstrated, which may be an important factor for the observation of ASD-like behaviors in adult mice at 60 days.

Effects of auriculotherapy on anxiety and biomarkers in Primary Health Care: a clinical trial / Efeitos da auriculoterapia na ansiedade e biomarcadores na Atenção Primária à Saúde: um ensaio clínico / Efectos de la auriculoterapia sobre la ansiedad y biomarcadores en Atención Primaria de Salud: un ensayo clínico

ABSTRACT Objective: to assess the effects of auriculotherapy on anxiety and brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) serum levels in adults assisted in Primary Health Care. Methods: a pre-experimental pilot clinical trial. Information was obtained from 19 patients using the State-Trait Anxiety Inventory (STAI) and analysis of BDNF, NSE and S100B serum levels. Results: the pre-intervention anxiety score in the IDATE-Trait was 52.11±6.691 (CV 12.84%) and the assessment after auriculotherapy was significantly lower (43.72±8.141; CV 18.62%; P=0.0007). S100B levels were significantly reduced after auriculotherapy (from 64.03±72.18 to 54.03±68.53 pg/mL; CV 126.8%; P=0.0023). Conclusion: auriculotherapy effectively reduced anxiety levels. It proved to be safe and easy to apply, allowing nurses to perform this technique autonomously. A reduction of S100B was also evidenced, demonstrating possible prevention of neuronal damage.

RESUMO Objetivo: avaliar os efeitos da auriculoterapia sobre a ansiedade e os níveis séricos do fator neurotrófico derivado do cérebro (BDNF), enolase-específica de neurônios (NSE) e proteína ligadora de cálcio S100B (S100B) em adultos atendidos na Atenção Primária à Saúde. Métodos: ensaio clínico piloto pré-experimental. As informações foram obtidas de 19 pacientes por meio do Inventário de Ansiedade Traço-Estado (IDATE) e da análise dos níveis séricos de BDNF, NSE e S100B. Resultados: o escore de ansiedade pré-intervenção no IDATE-Traço foi de 52,11±6,691 (CV 12,84%) e a avaliação após a auriculoterapia foi significativamente menor (43,72±8,141; CV 18,62%; P=0,0007). Os níveis de S100B foram significativamente reduzidos após auriculoterapia (de 64,03±72,18 para 54,03±68,53 pg/mL; CV 126,8%; P=0,0023). Conclusão: a auriculoterapia reduziu efetivamente os níveis de ansiedade. Mostrou-se segura e de fácil aplicação, possibilitando ao enfermeiro realizar esta técnica com autonomia. Uma redução de S100B também foi evidenciada, demonstrando possível prevenção de danos neuronais.

RESUMEN Objetivo: evaluar los efectos de la auriculoterapia sobre la ansiedad y los niveles séricos de factor neurotrófico derivado de cerebro (BDNF), enolasa-específica de neurona (NSE) y proteína fijadora de calcio S100B (S100B) en adultos atendidos en Atención Primaria de Salud. Métodos: ensayo clínico piloto preexperimental. Se obtuvo información de 19 pacientes mediante el Inventario de Ansiedad Estado-Rasgo (STAI) y análisis de niveles séricos de BDNF, NSE y S100B. Resultados: la puntuación de ansiedad preintervención en el IDATE-Rasgo fue de 52,11±6,691 (CV 12,84%) y la valoración tras la auriculoterapia fue significativamente menor (43,72±8,141; CV 18,62%; P=0,0007). Los niveles de S100B se redujeron significativamente después de la auriculoterapia (de 64,03±72,18 a 54,03±68,53 pg/mL; CV 126,8%; P=0,0023). Conclusión: la auriculoterapia redujo efectivamente los niveles de ansiedad. Demostró ser seguro y fácil de aplicar, lo que permitió a las enfermeras realizar esta técnica de forma autónoma. También se evidenció una reducción de S100B, lo que demuestra una posible prevención del daño neuronal.

The effect of modafinil on passive avoidance memory, brain level of BDNF and oxidative stress markers in sepsis survivor rats.

Propose/aim of study: Modafinil (MD) is a psychostimulant drug used off-label and cognitive dysfunction may be a significant emerging treatment target for this drug. The objective of this study was to evaluate the effect of MD on the neurochemical parameters and memory impairment of rats submitted to sepsis by cecal ligation and perforation (CLP).Material and method: Male Wistar rats (250-350g) were submitted to CLP, or sham as control, and divided into the sham + water, sham + MD (300 mg/kg), CLP + water, and CLP + MD (300 mg/kg) groups. Ten days after the administration of MD and CLP, the rats were submitted to a memory test by passive avoidance apparatus being sacrificed. The nitrite and nitrate (N/N) concentration, myeloperoxidase (MPO) and catalase (CAT) activity, lipid and protein oxidative damage, and brain-derived neurotrophic factor (BDNF) levels were measured in the prefrontal cortex and hippocampus.Results: The passive avoidance test verified an increase in the latency time compared training and test section in the groups sham + water and CLP + MD. Decreased N/N concentration and MPO activity were verified in the prefrontal cortex of rats submitted to CLP and MD treatment, as well as reduced protein and lipid oxidative damage in the hippocampus, which was accompanied by increased CAT activity and BDNF levels.Conclusion: Our data indicate the role of MD in attenuating oxidative stress parameters, the alteration of BDNF, and an improvement in memory impairment in rats ten days after induction of sepsis.

Gentle Touch Therapy, Pain Relief and Neuroplasticity at Baseline in Fibromyalgia Syndrome: A Randomized, Multicenter Trial with Six-Month Follow-Up.

BACKGROUND: Fibromyalgia (FM) is considered a stress-related disorder characterized mainly by chronic widespread pain. Its pathogenesis is unknown, but cumulative evidence points at dysfunctional transmitter systems and inflammatory biomarkers that may underlie the major symptoms of the condition. This study aimed to evaluate pain scores (primary outcome), quality of life, inflammatory biomarkers and neurotransmitter systems in women with FM (secondary outcomes) subjected to gentle touch therapy (GTT) or placebo. METHODS: A total of 64 female patients with FM were randomly assigned to two groups, namely GTT (n = 32) or Placebo (n = 32). Clinical assessments were conducted at baseline and post-intervention with six-month follow-up. We measured serum catecholamines (dopamine), indolamines and intermediary metabolites (serotonin or 5-hydroxyindolacetic acid (5-HIAA)), as well as tetrahydrobiopterin (BH4), which is a cofactor for the synthesis of neurotransmitters and inflammatory biomarkers in women with FM. A group of healthy individuals with no intervention (control group) was used to compare biochemical measurements. Intervention effects were analyzed using repeated measures (RM) two-way ANOVA followed by Bonferroni post hoc test and mixed ANCOVA model with intention to treat. RESULTS: Compared to placebo, the GTT group presented lower pain scores and brain-derived neurotrophic factor (BDNF) levels without altering the quality of life of women with FM. Changes in BDNF had a mediating role in pain. Higher baseline serum BDNF and 5-HIAA or those with a history of anxiety disorder showed a higher reduction in pain scores across time. However, women with higher serum dopamine levels at baseline showed a lower effect of the intervention across the observation period revealed by an ANCOVA mixed model. CONCLUSIONS: In conclusion, lower pain scores were observed in the GTT group compared to the placebo group without altering the quality of life in women with FM. Reductions in BDNF levels could be a mechanism of FM pain status improvement. In this sense, the present study encourages the use of these GTT techniques as an integrative and complementary treatment of FM.

Iota-carrageenan/xyloglucan/serine powders loaded with tranexamic acid for simultaneously hemostatic, antibacterial, and antioxidant performance.

This study sought to prepare powder hemostats based on iota-carrageenan (ιC), xyloglucan (XYL), l-serine (SER), and tranexamic acid (TA). The powder form was chosen because it enables the hemostat to be used in wounds of any shape and depth. The powder hemostats showed irregular shapes and specific surface areas ranging from 34 to 46 m2/g. Increasing TA amount decreases the specific surface area, bulk density, water and blood absorption, and the antibacterial activities of the powder hemostats, but not the water retention ability. Conversely, in vitro biodegradation was positively impacted by increasing the TA content in the powder hemostats. In both the in vitro and in vivo tests, powder hemostats showed reduced bleeding time, significant adhesion of red blood cells, great hemocompatibility, moderate antioxidant activity, and high biocompatibility. These findings shed new light on designing powder hemostats with intrinsic antibacterial and antioxidant activity and excellent hemostatic performance.

Diabetes Exacerbates Sepsis-Induced Neuroinflammation and Brain Mitochondrial Dysfunction.

Sepsis is a life-threatening organ dysfunction, which demands notable attention for its treatment, especially in view of the involvement of immunodepressed patients, as the case of patients with diabetes mellitus (DM), who constitute a population susceptible to develop infections. Thus, considering this endocrine pathology as an implicatory role on the immune system, the aim of this study was to show the relationship between this disease and sepsis on neuroinflammatory and neurochemical parameters. Levels of IL-6, IL-10, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and mitochondrial respiratory chain complexes were evaluated in the hippocampus and prefrontal cortex 24 h after sepsis by cecal ligation and perforation (CLP) in Wistar rats induced to type 1 diabetes by alloxan (150 mg/kg). It was verified that diabetes implied immune function after 24 h of sepsis, since it contributed to the increase of the inflammatory process with higher production of IL-6 and decreased levels of IL-10 only in the hippocampus. In the same brain area, a several decrease in NGF level and activity of complexes I and II of the mitochondrial respiratory chain were observed. Thus, diabetes exacerbates neuroinflammation and results in mitochondrial impairment and downregulation of NGF level in the hippocampus after sepsis.

Preventive Supplementation of Omega-3 Reduces Pain and Pro-inflammatory Cytokines in a Mouse Model of Complex Regional Pain Syndrome Type I.

Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1ß concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals' locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.

Immunoregulatory Effect of Preventive Supplementation of Omega-3 Fatty Acid in a Complex Regional Pain Syndrome Type I Model in Mice.

Objective: Complex regional pain syndrome (CRPS) is usually triggered by trauma or a surgical procedure, and it typically becomes an established one after an intense inflammatory process with chronic pain and edema as the main symptoms. Available treatments for CRPS have low efficacy. This study aimed to evaluate the clinical and immunoregulatory effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation on paw edema and anti- and pro-inflammatory cytokines and macrophage phenotypes in the chronic post-ischemia pain (CPIP) preclinical model of CRPS-Type I. Methods: Female Swiss mice were supplemented with omega-3, corn oil, or saline and then submitted to the CPIP model of ischemia/reperfusion (I/R) injury. Supplementation was carried out for 30 days prior to and up to 2 or 15 days after the induction of CPIP, according to experimental protocols. The supplementation protocol included 1,500 mg/kg of omega-3 or corn oil through an intragastric route (gavage). Paw edema, interleukin- (IL-) 4, IL-10, transforming growth factor-ß1 (TGF-ß1), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF) were then measured in the paw skin and muscle by enzyme-linked immunosorbent assay (ELISA), and macrophage phenotypes (M1 and M2) assessed in the paw muscle by Western blotting. Results: The CPIP model induced an increase in paw thickness up to 72 h post-I/R. Mice supplemented with omega-3 compared to the saline group displayed reduced edema but neither altered skin IL-4 or skin and muscle TGF-ß1, TNF, and MCP-1 concentrations, nor did they exhibit significantly altered muscle macrophage phenotype on the 2nd-day post-CPIP. However, omega-3 supplementation reversed the I/R-related reduction in IL-4 in the paw muscle compared to groups supplemented with saline and corn oil. Furthermore, omega-3 promoted the reduction of IL-10 levels in the paw skin, compared to animals with lesions supplemented with saline, until the 2nd-day post-CPIP. On the 15th day post-CPIP, IL-10 was significantly increased in the muscle of animals supplemented with omega-3 compared to the saline group. Conclusion: The results suggest that omega-3 PUFA supplementation has anti-inflammatory effects in the CPIP model of CRPS-Type I, significantly reducing paw edema and regulating concentrations of anti-inflammatory cytokines, including IL-4 and IL-10.