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Background and objectives: The neurodevelopment of the offspring is suggested to be influenced by the maternal immune system's responses throughout pregnancy, which in turn is also vulnerable to maternal psychosocial stress conditions. Therefore, our main goal was to investigate whether maternal peripheral immunological biomarkers (IB) during two stages of gestation are associated with distinct neurodevelopmental trajectories in the first two years of life. As a second goal, we also explored the association between maternal distal (childhood) and proximal (gestation) stressful experiences and the immunological markers assessed during pregnancy. Methods: Maternal childhood trauma, depressive and anxiety symptoms, and peripheral IB (IFNγ, IL-10, IL1ß, IL6, IL8, TNFα, EGF, IL13, IL17, IL1Ra and IL4) were measured at baseline (8-16 weeks of pregnancy) and at 30 weeks of pregnancy in 160 women. The participants had the blood samples collected from two randomized clinical trials conducted by the same team and methods in the same community. A Principal Component Analysis (PCA) was implemented to create meaningful composite variables that describe the cytokines joint variation. Finally, linear mixed-effects modeling was used to investigate the influence of inflammatory biomarkers, maternal childhood trauma, anxiety, and depressive symptoms on Bayley's III scores trajectories. Results: The IB profile during the 3rd trimester of pregnancy predicted the offspring's neurodevelopmental trajectories in the first two years of life. The components derived from PCA were important predictors and captured different immune responses, reflecting both pro- and anti-inflammatory states. Maternal stressful experiences did not correlate with the immunological markers. Although not a reliable predictor alone, maternal psychosocial stress at the 1st trimester of pregnancy interacted with the mother's immune response while predicting the neurodevelopmental scores during the first two years of life. Conclusions: Our results underscore the importance of the maternal immune response during pregnancy in shaping the neurodevelopmental trajectory of the offspring. Additionally, we observed that the maternal distress at the early stages of pregnancy has an incremental effect on the neurodevelopmental outcome but depends upon the immune response.

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Maladaptive avoidance behaviour is often observed in patients suffering from anxiety and trauma- and stressor-related disorders. The prefrontal-amygdala-hippocampus network is implicated in learning and memory consolidation. Neuroinflammation in this circuitry alters network dynamics, resulting in maladaptive avoidance behaviour. The two-way active avoidance test is a well-established translational model for assessing avoidance responses to stressful situations. While some animals learn the task and show adaptive avoidance (AA), others show strong fear responses to the test environment and maladaptive avoidance (MA). Here, we investigated if a distinct neuroinflammation pattern in the prefrontal-amygdala-hippocampus network underlies the behavioural difference observed in these animals. Wistar rats were tested 8 times and categorized as AA or MA based on behaviour. Brain recovery followed for the analysis of neuroinflammatory markers in this network. AA and MA presented distinct patterns of neuroinflammation, with MA showing increased astrocyte, EAAT-2, IL-1ß, IL-17 and TNF-ɑ in the amygdala. This neuroinflammatory pattern may underlie these animals' fear response and maladaptive avoidance. Further studies are warranted to determine the specific contributions of each inflammatory factor, as well as the possibility of treating maladaptive avoidance behaviour in patients with psychiatric disorders with anti-inflammatory drugs targeting the amygdala.

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Objectives: Bisphosphonates (BFs) show clinical effectiveness in managing osteoporosis and bone metastases but pose risks of bisphosphonate-related jaw osteonecrosis (BRONJ). With no established gold standard for BRONJ treatment, our focus is on symptom severity reduction. We aimed to assess the preventive effects of bioactive glass and/or pericardial membrane in a preclinical BRONJ model, evaluating their potential to prevent osteonecrosis and bone loss post-tooth extractions in zoledronic acid (ZA)-treated animals. Methods: Rats, receiving ZA or saline biweekly for four weeks, underwent 1st and 2nd lower left molar extractions. Pericardial membrane alone or with F18 bioglass was applied post-extractions. Microarchitecture analysis and bone loss assessment utilized computerized microtomography (CT) and positron emission tomography (PET) with 18F-FDG and 18F-NaF tracers. Histological analysis evaluated bone injury. Results: Exclusive alveolar bone loss occurred post-extraction in the continuous ZA group, inducing osteonecrosis, osteolysis, osteomyelitis, and abscess formation. Concurrent pericardial membrane with F18 bioglass application prevented these outcomes. Baseline PET/CT scans showed no discernible uptake differences, but post-extraction 18F-FDG tracer imaging revealed heightened glucose metabolism at the extraction site in the ZA-treated group with membrane, contrasting the control group. Conclusion: These findings suggest pericardial membrane with F18 bioglass effectively prevents BRONJ in the preclinical model.

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Pain control after deep brain stimulation (DBS) in Parkinson's disease (PD) remains unclear. Following six months, subthalamic (STN)-DBS reduced sensory complaints related to parkinsonism and bodily discomfort, increasing central beta-endorphin level. Pallidal GPi-DBS decreased bodily discomfort and beta-endorphin levels. Unexplained pain by other conditions and bodily discomfort were negatively correlated with beta-endorphin levels. Thus, DBS regulates central opioids, and prioritizing STN is important for PD patients with significant sensory complications.

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Brazil has great biodiversity, and the Amazon biome stands out for a variety of native fruits with high economic and nutritional potential. Murici (Byrsonima crassifolia) and taperebá (Spondias mombin) are sources of vitamins, minerals, and phytochemicals with potential health benefits. Because of the bioactive potential of these Brazilian fruits, this review aims to gather the most current existing knowledge about their botanical, nutritional, and phytochemical properties, because the presence of several bioactive compounds may bring promising strategies to the prevention and treatment of several diseases. The search was conducted of the LILACS, MEDLINE, PubMed, and Science Direct databases, considering articles published between 2010 and 2023. The compiled results showed that these fruits, their leaves, and seeds have great antioxidant activity and are a good source of phytochemicals, especially phenolic compounds. In vitro and in vivo studies indicate that these bioactive compounds have several health benefits related to the prevention or treatment of diseases, including antioxidant effects; anti-inflammatory effects; and antidiabetic, antidepressant, neuroprotective, antiproliferative, anticancer, hypolipemic, cardioprotective, gastroprotective, hepatoprotective, and nephroprotective effects, and they are particularly related to the reduction of damage from oxidative stress. This review highlights the potential of these fruits as functional foods and for therapeutic purposes. However, it is recommended to conduct more studies on the identification and quantification of phytochemicals present in these fruits and studies in humans to better understand the mechanisms of action related to their effects and to understand the interaction of these compounds with the human body, as well as to prove the safety and efficacy of these compounds on health.

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This study evaluates the effects of supplementation of murici (Byrsonima crassifolia) and taperebá (Spondias mombin) pulp extracts on dietary intake, body composition, biochemical parameters, and markers of oxidative stress. Two experiments were conducted with a total of 80 healthy male Wistar rats and a 30-day supplementation. In the first experiment, animals were divided into control (C) group, murici group 50 mg/(kg⸱day) (50Mu), murici group 100 mg/(kg⸱day) (100Mu), and murici group 200 mg/(kg⸱day) (200Mu). In the second experiment, animals were divided into C group, taperebá group 50 mg/(kg⸱day) (50Tap), taperebá group 100 mg/(kg⸱day) (100Tap), and taperebá group 200 mg/(kg⸱day) (200Tap). Results showed lower feed intake in 50Mu, 100Mu, and 100Tap groups (13%, 12%, and 10%, respectively, P < .05) and lower body fat in 200Mu, 100Tap, and 200Tap groups (16.0%, 29.1%, and 27.1%, respectively, P < .05). Only the 100Tap group showed reduced adipose tissue content (30.4%; P < .05). Increased plasma antioxidant capacity was observed at all doses for both fruits. Taperebá supplementation reduced ferrous oxidation-xylenol orange levels (50Tap: 8.4%, 100Tap: 16.1%, 200Tap: 24.3%; P < .05) and increased thiol levels (50Tap: 39%, 100Tap: 31%; P < .05). Serum thiobarbituric acid reactive substances levels were reduced in all groups receiving taperebá (50Tap: 77.7%, 100Tap: 73.1%, 200Tap: 73.8%; P < .05) and murici (50Mu: 44.5%, 100Mu: 34%, 200Mu: 43%; P < .05). Therefore, it is suggested that the inclusion of these fruits in the diet can contribute to health maintenance and disease prevention, through their effects on controlling food intake, improving body composition, and in combating oxidative stress.

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Background: Conventional thoracotomy (CT) often leads to systemic inflammatory response syndrome (SIRS), which induces several clinical complications. CT remains widely used in low-income institutions. Although minimally invasive surgical procedures, such as robotic surgery (RS), have been used to prevent many of the complications inherit from the surgical procedure. Here, we investigated the protective effect of vagus nerve stimulation (VNS) in a pre-clinical model during CT or RS and postoperative period (POP) relative to clinical complications and inflammatory control. The objective was to compare hemodynamic features and cytokine levels in the blood, lung, and bronchoalveolar lavage (BAL) fluids of animals subjected to CT or RS with or without VNS. Methods: Twenty-four minipigs were subjected to 12 animals CT and 12 animals RS, with or without VNS, and accompanied 24 h later by pulmonary lobectomy. Blood samples for evaluating the hemodynamic parameters were collected before the surgical preparation, immediately after the beginning of VNS, and every 4 h until 24 h after the lobectomy. BAL fluid and lung tissue were collected at the end of the experiment. Cytokine levels were evaluated in the blood, BAL fluid, and lung tissues. Results: VNS maintained a more stable heart rate during POP and decreased the incidence of overall cardiac complications while preventing increase in IL-6 levels 12 h after lobectomy, compared to sham animals. No differences were found in cytokine expression in the BAL fluid and lung tissue in any of the studied groups. Conclusions: Taken together, our data suggested that VNS should be considered a non-pharmacological tool in the prevention of the exacerbated inflammatory response responsible for severe clinical complications, especially in more aggressive surgical procedures.

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Understanding the mechanisms responsible for anxiety disorders is a major challenge. Avoidance behavior is an essential feature of anxiety disorders. The two-way avoidance test is a preclinical model with two distinct subpopulations-the good and poor performers-based on the number of avoidance responses presented during testing. It is believed that the habenula subnuclei could be important for the elaboration of avoidance response with a distinct pattern of activation and neuroinflammation. The present study aimed to shed light on the habenula subnuclei signature in avoidance behavior, evaluating the pattern of neuronal activation using FOS expression and astrocyte density using GFAP immunoreactivity, and comparing control, good and poor performers. Our results showed that good performers had a decrease in FOS immunoreactivity (IR) in the superior part of the medial division of habenula (MHbS) and an increase in the marginal part of the lateral subdivision of lateral habenula (LHbLMg). Poor performers showed an increase in FOS in the basal part of the lateral subdivision of lateral habenula (LHbLB). Considering the astroglial immunoreactivity, the poor performers showed an increase in GFAP-IR in the inferior portion of the medial complex (MHbl), while the good performers showed a decrease in the oval part of the lateral part of the lateral complex (LHbLO) in comparison with the other groups. Taken together, our data suggest that specific subdivisions of the MHb and LHb have different activation patterns and astroglial immunoreactivity in good and poor performers. This study could contribute to understanding the neurobiological mechanisms responsible for anxiety disorders.

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Breast cancer is the second most common diagnosed type of cancer in women. Chronic neuropathic pain after mastectomy occurs frequently and is a serious health problem. In our previous single-center, prospective, randomized controlled clinical study, we demonstrated that the combination of serratus anterior plane block (SAM) and pectoral nerve block type I (PECS I) with general anesthesia reduced acute postoperative pain. The present report describes a prospective follow-up study of this published study to investigate the development of chronic neuropathic pain 12 months after mastectomy by comparing the use of general anesthesia alone and general anesthesia with SAM + PECS I. Additionally, the use of analgesic medication, quality of life, depressive symptoms, and possible correlations between plasma levels of interleukin (IL)-1 beta, IL-6, and IL-10 collected before and 24 h after surgery as predictors of pain and depression were evaluated. The results showed that the use of SAM + PECS I with general anesthesia reduced numbness, hypoesthesia to touch, the incidence of patients with chronic pain in other body regions and depressive symptoms, however, did not significantly reduce the incidence of chronic neuropathic pain after mastectomy. Additionally, there was no difference in the consumption of analgesic medication and quality of life. Furthermore, no correlation was observed between IL-1 beta, IL-6, and IL-10 levels and pain and depression. The combination of general anesthesia with SAM + PECS I reduced the occurrence of specific neuropathic pain descriptors and depressive symptoms. These results could promote the use of SAM + PECS I blocks for the prevention of specific neuropathic pain symptoms after mastectomy.Registration of clinical trial: The Research Ethics Board of the Hospital Sirio-Libanes/Brazil approved the study (CAAE 48721715.0.0000.5461). This study is registered at Registro Brasileiro de Ensaios Clinicos (ReBEC), and ClinicalTrials.gov, Identifier: NCT02647385.

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BACKGROUND: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. METHODS: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. RESULTS: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r2 = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r2 = 0.4, p = 0.005), and striatum (positive correlation, r2 = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. CONCLUSIONS: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.

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Resumen Desde la perspectiva de género, la heteronormatividad en el deporte genera desigualdades que afectan a las minorías sexuales como el colectivo trans. El objetivo de este trabajo es identificar barreras generadoras de discriminación y exclusión durante la práctica deportiva en personas transgénero. Los participantes de este estudio son cuatro personas trans, mayores de edad y con experiencia en la práctica deportiva. Se ha utilizado como técnica de investigación una entrevista en profundidad diseñada para esta investigación. Tras realizar el correspondiente análisis de contenidos, son cuatro las categorías identificadas como barreras por los participantes del estudio. Como principal conclusión, se ha establecido la necesidad de investigar y recopilar datos de este colectivo para ahondar en el conocimiento de su problemática y para generar información y formación disponible dirigida a los agentes socioeducativos que configuran la organización y desarrollo del deporte.

Resumo Do ponto de vista de gênero, a heteronormatividade no esporte gera desigualdades que afetam as minorias como o coletivo trans. O objetivo deste trabalho é identificar as barreiras que criam a discriminação e exclusão de pessoas transgênero durante as atividades esportivas. Os participantes deste estudo são quatro pessoas trans, maiores de idade e com experiências na prática esportiva. Foi utilizada como técnica de investigação uma entrevista desenhada para esta pesquisa. Realizada a análise dos conteúdos correspondentes, foram identificadas quatro categorias como barreiras pelos participantes do estudo. Como conclusão principal, foi estabelecida a necessidade de investigar e coletar dados desse coletivo para aprofundar o conhecimento, sua problemática e gerar informação e formação disponível dirigida para os agentes socioeducativos que configuram na organização e desenvolvimento do esporte.

Abstract From a gender perspective, heteronormativity in sport generates inequalities that affect sexual minorities such as the trans group. The aim of this paper is to identify barriers that generate discrimination and exclusion during the sport practice for transgender people. The participants of this study are four transgender people, who are adults and have experience in sports practice. An in-depth interview designed for this research has been used as a research technique. After carrying out the corresponding content analysis, there are four categories identified by the study participants as barriers. As a main conclusion, the need to investigate and collect data regarding this group has been established to delve into the knowledge of their problems, as well as to generate information and available training aimed at the socio-educational agents that make up the organization and development of sport.

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Posterior hypothalamic-deep brain stimulation (pHyp-DBS) has been reported as a successful treatment for reducing refractory aggressive behaviors in patients with distinct primary diagnoses. Here, we report on a patient with cri du chat syndrome presenting severe self-injury and aggressive behaviors toward others, who was treated with pHyp-DBS. Positive results were observed at long-term follow-up in aggressive behavior and quality of life. Intraoperative microdialysis and imaging connectomics analysis were performed to investigate possible mechanisms of action. Our results suggest the involvement of limbic and motor areas and alterations in main neurotransmitter levels in the targeted area that are associated with positive results following treatment.

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.

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Pain and depression are complex disorders that frequently co-occur, resulting in diminished quality of life. The habenula is an epithalamic structure considered to play a pivotal role in the neurocircuitry of both pain and depression. The habenula can be divided into two major areas, the lateral and medial habenula, that can be further subdivided, resulting in 6 main subregions. Here, we investigated habenula activation patterns in a rat model of neuropathic pain with accompanying depressive-like behaviour. Wistar rats received active surgery for the development of neuropathic pain (chronic constriction injury of the sciatic nerve; CCI), sham surgery (surgical control), or no surgery (behavioural control). All animals were evaluated for mechanical nociceptive threshold using the paw pressure test and depressive-like behaviour using the forced swimming test, followed by evaluation of the immunoreactivity to cFos-a marker of neuronal activity-in the habenula and subregions. The Open Field Test was used to evaluate locomotor activity. Animals with peripheral neuropathy (CCI) showed decreased mechanical nociceptive threshold and increased depressive-like behaviour compared to control groups. The CCI group presented decreased cFos immunoreactivity in the total habenula, total lateral habenula and lateral habenula subregions, compared to controls. No difference was found in cFos immunoreactivity in the total medial habenula, however when evaluating the subregions of the medial habenula, we observed distinct activation patterns, with increase cFos immunoreactivity in the superior subregion and decrease in the central subregion. Taken together, our data suggest an involvement of the habenula in neuropathic pain and accompanying depressive-like behaviour.

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BACKGROUND: Hemidystonia (HD) is characterized by unilateral involuntary torsion movements and fixed postures of the limbs and face. It often develops after deleterious neuroplastic changes secondary to injuries to the brain. This condition usually responds poorly to medical treatment, and deep brain stimulation often yields unsatisfactory results. We propose this study based on encouraging results from case reports of patients with HD treated by ablative procedures in the subthalamic region. OBJECTIVE: To compare the efficacy of stereotactic-guided radiofrequency lesioning of the subthalamic area vs available medical treatment in patients suffering from acquired HD. METHODS: This is an open-label study in patients with secondary HD allocated according to their treatment choice, either surgical or medical treatment; both groups were followed for one year. Patients assigned in the surgical group underwent unilateral campotomy of Forel. The efficacy was assessed using the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, Arm Dystonia Disability Scale, and SF-36 questionnaire scores. RESULTS: Patients in the surgical group experienced significant improvement in the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, and Arm Dystonia Disability Scale (39%, 35%, and 15%, respectively) 1 year after the surgery, with positive reflex in quality-of-life measures, such as bodily pain and role-emotional process. Patients kept on medical treatment did not experience significant changes during the follow-up. No infections were recorded, and no neurological adverse events were associated with either intervention. CONCLUSION: The unilateral stereotaxy-guided ablation of Forel H1 and H2 fields significantly improved in patients with HD compared with optimized clinical treatment.

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OBJECTIVES: A systematic review was performed to analyze the current evidence on three-dimensional (3D) computed tomography (CT) superimposition protocols used to assess dentomaxillofacial changes after orthognathic and orthofacial surgery. Accuracy, reproducibility, and efficiency were evaluated. METHODS: The search was divided into Main Search (PubMed, EMBASE, Cochrane Library, LILACS, and SciELO), Grey Literature search (Google Scholar and Open Grey), and Manual search. Thirteen studies were included. Of these, 10 reported data on accuracy, 10 on reproducibility and five on efficiency. Seven proposed or evaluated methods of voxel-based superimposition, three focused on the surface-based technique, one compared surface- and voxel-based superimposition protocols, one used the maximum mutual information algorithm, and one described a landmark-based superimposition method. Cone-beam computed tomography (CBCT) was the most common imaging technique, being used in 10 studies. RESULTS: The accuracy of most methods was high, showing mean differences smaller than voxels' dimensions, ranging between 0.05 and 1.76 mm for translational accuracy, and 0.10-1.09° for rotational accuracy. The overall reproducibility was considered good as demonstrated by the small mean error (range: 0.01-0.26 mm) and high correlation coefficients (range: 0.53-1.00). Timing to complete virtual superimposition techniques ranged between a few seconds up to 40 min. CONCLUSIONS: Voxel-based superimposition protocols presented the highest accuracy and reproducibility. Moreover, superimposition protocols that used automated processes and involved only one software were the most efficient.

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the goldstandard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.

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BACKGROUND: Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatric patients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation. OBJECTIVE: To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation. METHODS: This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI). RESULTS: Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas. CONCLUSION: These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.

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Intermittent Explosive Disorder (IED) is a psychiatric disorder characterized by recurrent outbursts of aggressive behaviour. Deep brain stimulation (DBS) in the posteromedial nucleus of the hypothalamus (pHyp) is an alternative therapy for extreme cases and shows promising results. Intraoperative microdialysis can help elucidate the neurobiological mechanism of pHyp-DBS. Objective To evaluate efficacy and safety of pHyp-DBS using eight-contact directional leads in patients with refractory IED (rIED) and the accompanying changes in neurotransmitters. Methods A prospective study in which patients with a diagnosis of rIED were treated with pHyp-DBS for symptom alleviation. Bilateral pHyp-DBS was performed with eight-contact directional electrodes. Follow-up was performed at 3, 6 and 12 months after surgery. Results Four patients (3 men, mean age 27 ± 2.8 yr) were included. All patients were diagnosed with rIED and severe intellectual disability. Two patients had congenital rubella, one has co-diagnosis of infantile autism and the fourth presents with drug-resistant epilepsy. There was a marked increase in the levels of GABA and glycine during intraoperative stimulation. The average improvement in aggressive behaviour in the last follow-up was 6 points (Δ: 50%, p= 0.003) while also documenting an important improvement of the SF-36 in all domains except bodily pain. No adverse events associated with pHyp-DBS were observed. Conclusions This is the first study to show the safety and beneficial effect of directional lead pHyp-DBS in patients with refractory Intermittent Explosive Disorder and to demonstrate the corresponding mechanism of action through increases in GABA and glycine concentration in the pHyp.

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Maize silage is used in the diet of dairy cows, with suitable results in milk yield. In this study, the composition and diversity of the bacterial communities of the silage process of Amarillo Zamorano (AZ) Mexican maize landrace with relation to the Antilope (A) commercial hybrid are described. From both types of maize, seeds were sown in experimental plots, plants harvested at the reproductive stage, chopped, and packed in laboratory micro-silos. Physicochemical parameters were evaluated, and DNA was extracted from the juice in the micro-silos. The bacterial communities were analyzed by next-generation sequencing (NGS) of seven hypervariable regions of the 16S rRNA gene. The composition of both bacterial communities was dominated by Lactobacillales and Enterobacteriales, Lactobacillales mainly in A silage and Enterobacteriales in AZ silage; as well, the core bacterial community of both silages comprises 212 operational taxonomic units (OTUs). Sugar concentration showed the highest number of significant associations with OTUs of different phyla. The structure of the bacterial communities was different in both silage fermentation processes, showing that AZ silage has a shorter fermentation process than A silage. In addition, NGS demonstrated the effect of the type of maize and local conditions on silage fermentation and contributed to potential strategies to improve the quality of AZ silage.