Europe PMC in 2020.

Europe PMC (https://europepmc.org) is a database of research articles, including peer reviewed full text articles and abstracts, and preprints - all freely available for use via website, APIs and bulk download. This article outlines new developments since 2017 where work has focussed on three key areas: (i) Europe PMC has added to its core content to include life science preprint abstracts and a special collection of full text of COVID-19-related preprints. Europe PMC is unique as an aggregator of biomedical preprints alongside peer-reviewed articles, with over 180 000 preprints available to search. (ii) Europe PMC has significantly expanded its links to content related to the publications, such as links to Unpaywall, providing wider access to full text, preprint peer-review platforms, all major curated data resources in the life sciences, and experimental protocols. The redesigned Europe PMC website features the PubMed abstract and corresponding PMC full text merged into one article page; there is more evident and user-friendly navigation within articles and to related content, plus a figure browse feature. (iii) The expanded annotations platform offers ∼1.3 billion text mined biological terms and concepts sourced from 10 providers and over 40 global data resources.

S100B protein: general characteristics and pathophysiological implications in the Central Nervous System.

BACKGROUND: Calcium-binding proteins are heterogeneous proteins that act binding this ion in specific domains, performing numerous functions. OBJECTIVE: In the present review, we aim to gather principal information about S100B protein in the Central Nervous System (CNS), highlighting its particularities, mapping, functionalities, and consequences on CNS dysfunction. METHODS: The research was carried out by searching Pubmed, Medline, Science Direct, Lilacs, the Cochrane Library, and Web of Science databases using the following descriptors: S100 protein; Central Nervous System; Nervous Lesions, as well as their corresponding terms in Portuguese and Spanish. The terms were first searched separately, then together. RESULTS: Due to its ability to bind with calcium, S100B is involved in the regulation of several intra- and extracellular physiological processes. As well as being multifunctional, this protein can be considered both a "marker" and "signaling" since it is capable of triggering functions of detection of and protection in situations of injury to the CNS. CONCLUSIONS: In-depth studies are necessary to discover the innumerable actions of this protein which are still unknown. It is expected that these can bring varied benefits by elucidating its therapeutic potential in preclinical and clinical situations.

Efficacy of cryotherapy in the treatment of cutaneous horn associated with papillomatosis in a dog.

Cutaneous horn is a skin disease with low incidence and few citations in the literature. This report describes a dog with multiple cutaneous lesions of papillomatosis and one giant cutaneous horn on the face. Two sessions of cryotherapy achieved complete remission of the lesions.

La corne cutanée est une maladie de la peau à faible incidence et peu citée dans la littérature. Cet article décrit un chien avec de multiples lésions cutanées de papillomatose et une corne cutanée géante sur la face. Deux séances de cryothérapie ont permis d'obtenir une rémission complète des lésions.

Los cuernos cutáneos son una lesion patológica de baja incidencia y con escasas menciones en la literatura. Este artículo describe un caso de un perro con multiples lesiones cutáneas de papilomatosis y un cuerno cutáneo gigante en la cara. Dos sesiones de crioterapia consiguieron una remisión completa de las lesiones.

O corno cutâneo é uma doença cutânea com baixa incidência e poucas citações na literatura. Este relato descreve um cão com múltiplas lesões cutâneas características de papilomatose e um corno cutâneo gigante na face. Houve remissão completa das lesões após duas sessões de crioterapia.

Behavioral and neurochemical effects of alpha lipoic acid associated with omega-3 in tardive dyskinesia induced by chronic haloperidol in rats.

Tardive dyskinesia (TD) is characterized by involuntary movements of the lower portion of the face being related to typical antipsychotic therapy. TD is associated with the oxidative imbalance in the basal ganglia. Lipoic acid (LA) and omega-3 (ω-3) are antioxidants acting as enzyme cofactors, regenerating antioxidant enzymes. This study aimed to investigate behavioral and neurochemical effects of supplementation with LA (100 mg/kg) and ω-3 (1 g/kg) in the treatment of TD induced by chronic use of haloperidol (HAL) (1 mg/kg) in rats. Wistar male rats were used, weighing between 180-200 g. The animals were treated chronically (31 days) with LA alone or associated with HAL or ω-3. Motor behavior was assessed by open-field test, the catalepsy test, and evaluation of orofacial dyskinesia. Oxidative stress was accessed by determination of lipid peroxidation and concentration of nitrite. LA and ω-3 alone or associated caused an improvement in motor performance by increasing locomotor activity in the open-field test and decreased the permanence time on the bar in the catalepsy test and decreased the orofacial dyskinesia. LA and ω-3 showed antioxidant effects, decreasing lipid peroxidation and nitrite levels. Thus, the use of LA associated with ω-3 reduced the extrapyramidal effects produced by chronic use of HAL.

Central effects of lipoic acid associated with paroxetine in mice.

Antidepressants, including selective serotonin reuptake inhibitors, are commonly prescribed for the treatment of affective disorders such as anxiety and depression. The purpose of this study was to investigate the central effects of acute administration of paroxetine (PXT) combined with lipoic acid (LA) on various behavioral models in mice. Paroxetine (10 and 20 mg/kg), LA (100 mg/kg), or vehicle was administered, intraperitoneally, 30 minutes before the tests. The results showed that PXT (10 mg/kg) alone and in combination with LA increased locomotor activity. In the anxiety models studied, an anxiolytic effect was observed after the administration of LA and PXT. In the tail suspension test, PXT at both doses and in combination with LA caused a significant decrease in immobility time. These results indicate possible anxiolytic and antidepressant effects of LA associated with PXT. These data suggest that coadministration of LA and PXT may improve anxiolytic and antidepressant responses, and being more effective than each drug alone. However, further studies are necessary to investigate the mechanism by which antioxidants exert antidepressant or anxiolytic action.

The Role of Vitamin D in the Treatment of Carpal Tunnel Syndrome: Clinical and Electroneuromyographic Responses.

Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.

Volumetric alterations in the basal ganglia in autism Spectrum disorder: A systematic review.

INTRODUCTION: Recent research indicates that some brain structures show alterations in conditions such as Autism Spectrum Disorder (ASD). Among them, are the basal ganglia that are involved in motor, cognitive and behavioral neural circuits. OBJECTIVE: Review the literature that describes possible volumetric alterations in the basal ganglia of individuals with ASD and the impacts that these changes have on the severity of the condition. METHODOLOGY: This systematic review was registered in the design and reported according to the PRISMA Items and registered in PROSPERO (CRD42023394787). The study analyzed data from published clinical, case-contemplate, and cohort trials. The following databases were consulted: PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials, using the Medical Subject Titles (MeSH) "Autism Spectrum Disorder" and "Basal Ganglia". The last search was carried out on February 28, 2023. RESULTS: Thirty-five eligible articles were collected, analyzed, and grouped according to the levels of alterations. CONCLUSION: The present study showed important volumetric alterations in the basal ganglia in ASD. However, the examined studies have methodological weaknesses that do not allow generalization and correlation with ASD manifestations.

Basal ganglia for beginners: the basic concepts you need to know and their role in movement control.

The basal ganglia are a subcortical collection of interacting clusters of cell bodies, and are involved in reward, emotional, and motor circuits. Within all the brain processing necessary to carry out voluntary movement, the basal nuclei are fundamental, as they modulate the activity of the motor regions of the cortex. Despite being much studied, the motor circuit of the basal ganglia is still difficult to understand for many people at all, especially undergraduate and graduate students. This review article seeks to bring the functioning of this circuit with a simple and objective approach, exploring the functional anatomy, neurochemistry, neuronal pathways, related diseases, and interactions with other brain regions to coordinate voluntary movement.

Feasibility and effect of high-intensity training on the progression of motor symptoms in adult individuals with Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: To determine the feasibility and effect of high-intensity interval training (HIIT) in individuals with Parkinson's and their effect on symptom modification and progression. METHODS: We conducted this systematic review following the Preferred Reporting Items for systematic review and meta-analysis (PRISMA). All studies were searched in seven databases: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, SPORTDiscus, Virtual Health Library (VHL) and SCOPUS in September 2020 and updated in June 2023. The risk of bias was assessed by the Cochrane Collaboration tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. We used standardized mean difference (SMD) with a 95% confidence interval (CI) and random effects models, as well as the non-parametric Cochran's Q test and I2 inconsistency test to assess heterogeneity. RESULTS: A total of 15 randomized clinical trials with 654 participants (mean age, 65.4 years). The majority of studies included high intensity training interventions versus moderate intensity, usual care, or control group. The meta-analysis comparing high-intensity exercise versus control group showed an improvement in the disease severity (MD = -4.80 [95%CI, -6.38; -3.21 high evidence certainty); maximum oxygen consumption (MD = 1.81 [95%CI, 0.36; 3.27] very low evidence certainty) and quality of life (MD = -0.54 [95%CI, -0.94; -0.13] moderate evidence certainty). The results showed that high-intensity exercise compared with moderate intensity exercise group showed a improve motor function and functional mobility measured by the TUG test (MD = -0.38 [95%CI, -0.91; 0.16] moderate evidence certainty) with moderate heterogeneity between studies. CONCLUSION: High-intensity exercise performed in both continuous and interval modes when compared with control groups may provide motor function benefits for individuals with Parkinson's disease. HIIT may be feasible, but the intensity of the exercise may influence individuals with Parkinson's disease. However, there was a lack of evidence comparing high intensity and moderate intensity for this population, as the results showed heterogeneity.

The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson's disease: a review.

ABSTRACT This work reviews the evidence of the mechanism of neuronal degeneration in Parkinson's disease (PD) and the neuroprotective effect of lipoic acid and its use in the treatment of PD. PD is characterized by slow and progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta, leading to reduction of the striatal dopaminergic terminals. It is known that several factors influence neuronal damage. Among these factors, oxidative stress, immune system activity, microglial cells, and apoptotic mechanisms are of major importance. Currently, several antioxidants have been studied with the aim of reducing/slowing the progression of neurodegenerative processes. Lipoic acid is considered a universal antioxidant because it is an amphipathic substance. Lipoic acid and its reduced form, dihidrolipoic acid, act against reactive oxygen species, reducing oxidative stress. Therefore, this antioxidant has been used in the treatment of many diseases, including a new perspective for the treatment of Parkinson's disease.

Neurobiological effects of forced swim exercise on the rodent hippocampus: a systematic review.

Forced swimming is a common exercise method used for its low cost and easy management, as seen in studies with the hippocampus. Since it is applied for varied research purposes many protocols are available with diverse aspects of physical intensity, time and periodicity, which produces variable outcomes. In the present study, we performed a systematic review to stress the neurobiological effects of forced swim exercise on the rodent hippocampus. Behavior, antioxidant levels, neurotrophins and inflammatory markers were the main topics examined upon the swimming effects. Better results among these analyses were associated with forced exercise at moderate intensity with an adaptation period and the opposite for continuous exhausting exercises with no adaptation. On further consideration, a standard swimming protocol is necessary to reduce variability of results for each scenario investigated about the impact of the forced swimming on the hippocampus.Forced swimming is a common exercise method used for its low cost and easy management, as seen in studies with the hippocampus. Since it is applied for varied research purposes many protocols are available with diverse aspects of physical intensity, time and periodicity, which produces variable outcomes. In the present study, we performed a systematic review to stress the neurobiological effects of forced swim exercise on the rodent hippocampus. Behavior, antioxidant levels, neurotrophins and inflammatory markers were the main topics examined upon the swimming effects. Better results among these analyses were associated with forced exercise at moderate intensity with an adaptation period and the opposite for continuous exhausting exercises with no adaptation. On further consideration, a standard swimming protocol is necessary to reduce variability of results for each scenario investigated about the impact of the forced swimming on the hippocampus.

L-linalool exerts a neuroprotective action on hemiparkinsonian rats.

Linalool (LIN) is a monoterpene, responsible for the aroma of essential oils in some species. It presents a sedative and anxiolytic potential, enhancing GABAergic currents and behaving as a benzodiazepine-type of drug. The objectives of the present work were to study the neuroprotective effects of LIN on a model of Parkinson's disease. For that, male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned, and 6-OHDA-lesioned and treated with LIN (25, 50, and 100 mg/kg, p.o.) for 2 weeks. Afterwards, the animals were subjected to behavioral tests (apomorphine-induced rotations, open field, and forced swimming tests). Then, the animals were euthanized, and the striatum, hippocampus, and prefrontal cortex were processed for neurochemistry (nitrite and lipoperoxidation measurements) and immunohistochemistry (TH and DAT) assays. The results were analyzed by ANOVA and Tukey's test for multiple comparisons and considered significant at p < 0.05. LIN significantly improved the behavioral alterations of the 6-OHDA-lesioned group, as evaluated by the apomorphine-induced rotations, open field, and forced swimming tests. In addition, LIN partially reversed the decreased DA, DOPAC, and HVA contents observed in the 6-OHDA-lesioned striatum. The untreated 6-OHDA group presented increased nitrite contents and lipoperoxidation in all the brain areas studied, and these changes were completely reversed after LIN treatments. Finally, LIN significantly prevented the reduction in TH and DAT expressions demonstrated in the right 6-OHDA-lesioned striatum. All these data strongly suggest that LIN presents a neuroprotective action in hemiparkinsonian rats, probably related to the drug anti-inflammatory and antioxidant activities.

Extracytoplasmic Function σ Factors Can Be Implemented as Robust Heterologous Genetic Switches in Bacillus subtilis.

In bacteria, the promoter specificity of RNA polymerase is determined by interchangeable σ subunits. Extracytoplasmic function σ factors (ECFs) form the largest and most diverse family of alternative σ factors, and their suitability for constructing genetic switches and circuits was already demonstrated. However, a systematic study on how genetically determined perturbations affect the behavior of these switches is still lacking, which impairs our ability to predict their behavior in complex circuitry. Here, we implemented four ECF switches in Bacillus subtilis and comprehensively characterized their robustness toward genetic perturbations, including changes in copy number, protein stability, or antisense transcription. All switches show characteristic dose-response behavior that varies depending on the individual ECF-promoter pair. Most perturbations had performance costs. Although some general design rules could be derived, a detailed characterization of each ECF switch before implementation is recommended to understand and thereby accommodate its individual behavior.

Haloperidol-Induced Preclinical Tardive Dyskinesia Model in Rats.

Haloperidol is a first-generation antipsychotic used in the treatment of psychoses, especially schizophrenia. This drug acts by blocking dopamine D2 receptors, reducing psychotic symptoms. Notwithstanding its benefits, haloperidol also produces undesirable impacts, in particular extrapyramidal effects such as tardive dyskinesia (TD), which limit the use of this and related drugs. TD is characterized by repetitive involuntary movements occurring after chronic exposure therapy with haloperidol. Symptoms most commonly manifest in the orofacial area and include involuntary movements, tongue protrusion, pouting lips, chewing in the absence of any object to chew, and facial grimacing. The most serious aspect of TD is that it may persist for months or years after drug withdrawal and is irreversible in some patients. This unit, aimed at facilitating the study of TD, describes methods to induce TD in rats using haloperidol, as well as procedures for evaluating the animals's TD-related symptoms. © 2019 by John Wiley & Sons, Inc.

Supplementation with Curcuma longa Reverses Neurotoxic and Behavioral Damage in Models of Alzheimer's Disease: A Systematic Review.

BACKGROUND: The formation of senile plaques and neurofibrillary tangles of the tau protein are the main pathological mechanism of Alzheimer's disease (AD). Current therapies for AD offer discrete benefits to the clinical symptoms and do not prevent the continuing degeneration of neuronal cells. Therefore, novel therapeutic strategies have long been investigated, where curcumin (Curcuma longa) has shown some properties that can prevent the deleterious processes involved in neurodegenerative diseases. OBJECTIVE: The aim of the present work is to review studies that addressed the effects of curcumin in experimental models (in vivo and in vitro) for AD. METHOD: This study is a systematic review conducted between January and June 2017, in which a consultation of scientific articles from indexed periodicals was carried out in Science Direct, United States National Library of Medicine (PubMed), Cochrane Library and Scielo databases, using the following descriptors: "Curcuma longa", "Curcumin" and "Alzheimer's disease". RESULTS: A total of 32 studies were analyzed, which indicated that curcumin supplementation reverses neurotoxic and behavioral damages in both in vivo and in vitro models of AD. CONCLUSION: The administration of curcumin in experimental models seems to be a promising approach in AD, even though it is suggested that additional studies must be conducted using distinct doses and through other routes of administration.

Aspidosperma pyrifolium Mart: neuroprotective, antioxidant and anti-inflammatory effects in a Parkinson's disease model in rats.

OBJECTIVES: Aspidosperma species are used for several diseases, especially for malaria in Brazil. Although the genus is object of pharmacological studies, almost none are found on Aspidosperma pyrifolium. We investigate neuroprotective, antioxidant and anti-inflammatory properties of the APSE-Aq fraction (benzoic acid glycosylated derivative) on Parkinson's disease model. METHODS: Male Wistar rats were subjected to a 6-hydroxydopamine injection into the right striatum and treated or not with APSE-Aq (100 or 200 mg/kg, p.o.). The sham-operated group was injected with saline. Two weeks later, animals were subjected to behavioural, neurochemical and immunohistochemical evaluation. The data were analysed by ANOVA and Tukey test. KEY FINDINGS: The APSE-Aq-treated group shows a partial recovery of behavioural changes as compared with the untreated-6-hydroxydopamine group. A partial recovery was also observed in nitrite contents and lipid peroxidation. APSE-Aq treatments significantly reversed decreases in striatal dopamine and metabolites in the untreated 6-hydroxydopamine group. Immunostainings for markers as tyrosine hydroxylase and dopamine transporter decreased in the untreated 6-hydroxydopamine group and values recovered after APSE-Aq treatments. Similar data were seen for TNF-alpha. CONCLUSION: APSE-Aq presents neuroprotective, antioxidant and anti-inflammatory activities. Considering that APSE-Aq is chemically related to salicylic acid, it may act on similar targets.

Corrigendum to "The Treadmill Exercise Protects against Dopaminergic Neuron Loss and Brain Oxidative Stress in Parkinsonian Rats".

[This corrects the article DOI: 10.1155/2017/2138169.].

S100 proteins and their implication in the thalamus: an integrative review / Las proteínas S100 y su implicación en el tálamo: una revisión integradora

SUMMARY: S100 proteins belong group of calcium-binding proteins and are present in physiological intracellular and extracellular regulatory activities, such as cell differentiation, and act in inflammatory and neoplastic pathological processes. Recently, its expressions in the nervous system have been extensively studied, seeking to elucidate its action at the level of the thalamus: A structure of the central nervous system that is part of important circuits, such as somatosensory, behavioral, memory and cognitive, as well as being responsible for the transmission and regulation of information to the cerebral cortex. This article is an integrative review of scientific literature, which analyzed 12 studies present in Pubmed. The analysis showed that the relationship of S100 proteins and the thalamus has been described in neoplastic processes, mental disorders, hypoxia, trauma, stress, infection, Parkinson's disease and epilepsy. In summary, it is possible to conclude that this protein family is relevant as a marker in processes of thalamic injury, requiring further studies to better understand its clinical, preclinical meanings and its prognostic value.

Las proteínas S100 pertenecen al grupo de proteínas fijadoras de calcio y están presentes en actividades reguladoras fisiológicas intracelulares y extracelulares, como la diferenciación celular, y actúan en procesos patológicos inflamatorios y neoplásicos. Recientemente, sus expresiones en el sistema nervioso han sido ampliamente estudiadas, buscando dilucidar su acción a nivel del tálamo: una estructura del sistema nervioso central que forma parte de importantes circuitos, como el somatosensorial, conductual, de memoria y cognitivo, así como además de ser responsable de la transmisión y regulación de la información a la corteza cerebral. Este artículo es una revisión integradora de la literatura científica, que analizó 12 estudios presentes en Pubmed. El análisis mostró que la relación de las proteínas S100 y el tálamo ha sido descrita en procesos neoplásicos, trastornos mentales, hipoxia, trauma, estrés, infección, enfermedad de Parkinson y epilepsia. En resumen, es posible concluir que esta familia de proteínas es relevante como marcador en procesos de lesión talámica, requiriendo más estudios para comprender mejor su significado clínico, preclínico y su valor pronóstico.

The Treadmill Exercise Protects against Dopaminergic Neuron Loss and Brain Oxidative Stress in Parkinsonian Rats.

Parkinson's disease (PD), a progressive neurological pathology, presents motor and nonmotor impairments. The objectives were to support data on exercise benefits to PD. Male Wistar rats were distributed into sham-operated (SO) and 6-OHDA-lesioned, both groups without and with exercise. The animals were subjected to treadmill exercises (14 days), 24 h after the stereotaxic surgery and striatal 6-OHDA injection. Those from no-exercise groups stayed on the treadmill for the same period and, afterwards, were subjected to behavioral tests and euthanized for neurochemical and immunohistochemical assays. The data, analyzed by ANOVA and Tukey post hoc test, were considered significant for p < 0.05. The results showed behavioral change improvements in the 6-OHDA group, after the treadmill exercise, evaluated by apomorphine rotational behavior, open field, and rota rod tests. The exercise reduced striatal dopaminergic neuronal loss and decreased the oxidative stress. In addition, significant increases in BDNF contents and in immunoreactive cells to TH and DAT were also observed, in striata of the 6-OHDA group with exercise, relatively to those with no exercise. We conclude that exercise improves behavior and dopaminergic neurotransmission in 6-OHDA-lesioned animals. The increased oxidative stress and decreased BDNF contents were also reversed, emphasizing the importance of exercise for the PD management.

Effect of FGF-2 and sciatic nerve grafting on ChAT expression in dorsal root ganglia neurons of spinal cord transected rats.

Neurotrophic factors and peripheral nerves are known to be good substrates for bridging CNS trauma. The involvement of fibroblast growth factor-2 (FGF-2) activation in the dorsal root ganglion (DRG) was examined following spinal cord injury in the rat. We evaluated whether FGF-2 increases the ability of a sciatic nerve graft to enhance neuronal plasticity, in a gap promoted by complete transection of the spinal cord. The rats were subjected to a 4mm-long gap at low thoracic level and were repaired with saline (Saline or control group, n=10), or fragment of the sciatic nerve (Nerve group, n=10), or fragment of the sciatic nerve to which FGF-2 (Nerve+FGF-2 group, n=10) had been added immediately after lesion. The effects of the FGF-2 and fragment of the sciatic nerve grafts on neuronal plasticity were investigated using choline acetyl transferase (ChAT)-immunoreactivity of neurons in the dorsal root ganglion after 8 weeks. Preservation of the area and diameter of neuronal cell bodies in dorsal root ganglion (DRG) was seen in animals treated with the sciatic nerve, an effect enhanced by the addition of FGF-2. Thus, the addition of exogenous FGF-2 to a sciatic nerve fragment grafted in a gap of the rat spinal cord submitted to complete transection was able to improve neuroprotection in the DRG. The results emphasized that the manipulation of the microenvironment in the wound might amplify the regenerative capacity of peripheral neurons.