Cannabidiol improves maternal obesity-induced behavioral, neuroinflammatory and neurochemical dysfunctions in the juvenile offspring.

Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established. We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams. Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus. CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes. Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.

Omega-3 Attenuates Disrupted Neurotransmission and Partially Protects Metabolic Dysfunction Caused by Obesity in Wistar Rats.

Omega-3 (n3) is a polyunsaturated fatty acid well known for its anti-inflammatory and neuroprotective properties. Obesity is linked to chronic inflammation that disrupts metabolism, the intestine physiology and the central nervous system functioning. This study aims to determine if n3 supplementation can interfere with the effects of obesity on the mitochondrial activity, intestinal barrier, and neurotransmitter levels in the brain of Wistar rats that received cafeteria diet (CAF). We examined adipose tissue, skeletal muscle, plasma, intestine, and the cerebral cortex of four groups: CT (control diet), CTn3 (control diet with n3 supplementation), CAF, and CAFn3 (CAF and n3). Diets were offered for 13 weeks, with n3 supplementation in the final 5 weeks. Adipose tissue Electron Transport Chain complexes I, II, and III showed higher activity in CAF groups, as did complexes III and IV in skeletal muscle. Acetate levels in plasma were reduced in CAF groups, and Lipopolysaccharide (LPS) was higher in the CAF group but reduced in CAFn3 group. Claudin-5 in the intestine was lower in CAF groups, with no n3 supplementation effect. In the cerebral cortex, dopamine levels were decreased with CAF, which was reversed by n3. DOPAC, a dopamine metabolite, also showed a supplementation effect, and HVA, a diet effect. Serotonin levels increased in the CAF group that received supplementation. Therefore, we demonstrate disturbances in mitochondria, plasma, intestine and brain of rats submitted to CAF and the potential benefit of n3 supplementation in endotoxemia and neurotransmitter levels.

Effects of omega-3 supplementation on anxiety-like behaviors and neuroinflammation in Wistar rats following cafeteria diet-induced obesity.

ABSTRACTObjetives: Omega-3 (n3) fatty acids have been studied as an option to alleviate the harmful effects of obesity. However, its role in obesity-related behavioral changes is still controversial. This study aimed to evaluate the effects of n3 on behavior and neuroinflammation in obese animals. Methods: Male Wistar rats were divided into four groups: control diet (CT), CT+n3, cafeteria diet (CAF), and CAF+n3. Diet was administered for 13 weeks, and n3 was supplemented during the last 5 weeks. Metabolic and biochemical parameters were evaluated, as well as anxiety-like behaviors. Immunoblots were conducted in the animals' cerebral cortex and hippocampus to assess changes in neuroinflammatory markers.Results: CAF-fed animals showed higher weight gain, visceral adiposity, fasting glucose, total cholesterol, triglycerides, and insulin levels, and n3 improved the lipid profile and restored insulin sensitivity. CAF-fed rats showed anxiety-like behaviors in the open field and light-dark box tasks but not in the contextual aversive conditioning. Omega-3 did not exert any effect on these behaviors. Regarding neuroinflammation, diet and supplementation acted in a region-specific manner. In the hippocampus, CAF reduced claudin-5 expression with no effect of n3, indicating a brain-blood barrier disruption following CAF. Furthermore, in the hippocampus, the glial fibrillary acidic protein (GFAP) and toll-like receptor 4 (TLR-4) were reduced in treated obese animals. However, n3 could not reverse the TLR-4 expression increase in the cerebral cortex.Discussion: Although n3 may protect against some neuroinflammatory manifestations in the hippocampus, it does not seem sufficient to reverse the increase in anxiolytic manifestations caused by CAF.

Integrating PET chemical recycling with pyrolysis of mixed plastic waste via pressureless alkaline depolymerization in a hydrocarbon solvent.

This study presents a proof of concept for a technology train that integrates polyethylene terephthalate (PET) recovery from mixed plastic waste and plastic pyrolysis. PET is depolymerized into terephthalic acid (TPA) by hydrolysis using a low volatility oil as medium, which enables (i) low-pressure operation, and (ii) a selective separation and recovery of TPA from the product mix by a simple process of filtration, washing, and precipitation. Full PET conversion and high TPA recovery (>98 %) were achieved at 260 °C. This technology train is demonstrated to be effective for processing mixed waste streams, leading to higher yield and quality of liquid product from thermal pyrolysis when compared with feedstock that has not been pre-treated. Further, the technology could be readily integrated with a plastics pyrolysis process, whereby a by-product from the pyrolysis could be used as the low-volatility oil.

Calorie restriction mitigates metabolic, behavioral and neurochemical effects of cafeteria diet in aged male rats.

Besides metabolic dysfunctions, elderly individuals with obesity are at special risk of developing cognitive decline and psychiatric disturbances. Restricted calorie consumption could be an efficient strategy to improve metabolic function after obesity. However, its effects on anxiety-like behaviors in aged rats submitted to an obesogenic diet are unknown. For this purpose, 42 Wistar rats (18-months old) were divided into four groups: Control (CT), calorie restriction (CR), cafeteria diet (CAF), and CAF+CR (CAF/CR). CT, CR, and CAF groups received the diets for 8 weeks. CAF/CR group was submitted to the CAF menu for 7 weeks and then switched to a standard diet on a CR regimen, receiving 30% lower calories than consumed by the CT, for another 5 weeks. CAF's menu consisted of ultra-processed foods such as cookies, chocolate, sausage, and bologna. Body weight, visceral adiposity, and biochemical blood analysis were evaluated for obesity diagnosis. The profile of gut microbiota was investigated, along with circulating levels of LPS. Neurochemical parameters, such as neurotransmitter levels, were dosed. Anxiety-like behaviors were accessed using open field (OF) and elevated plus maze (EPM) tests. As expected, CR reduced weight gain and improved glucose homeostasis. Gut microbiome disturbance was found in CAF-fed animals accompanied by increased levels of LPS. However, CR after CAF mitigated several harmful responses. The obesogenic diet triggered anxiety-like manifestations in the OF and EPM tests that were not evidenced in the CAF/CR group. These findings indicate that CR can be a promising strategy for the neurological effects of obesity in aged rats.

Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity.

Introduction: The implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed. Methods: Here we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats. Results: We have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1ß in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to in utero neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes. Discussion: Together, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.

Stroke-related mortality analysis in Paraná, Brazil, over 10 years.

BACKGROUND: Stroke is the second leading cause of death and disability around the world. OBJECTIVE: The purpose of this study is to evaluate the age- and sex-specific mortality rates related to stroke in the state of Paraná, Brazil, between 2007 and 2016. METHODS: In this cross-sectional study, residents in the state of Paraná were selected by death certificates (from 2007-2016); the basic cause of death was stroke. A descriptive analysis was performed, and mortality rates were calculated with a 95% confidence interval (95% CI) for each year. RESULTS: From 2007 to 2016, there were 62,607 deaths in the state of Paraná due to stroke. Most individuals had medical assistance before death (85.7% in 2007 versus 83.9% in 2016), and most of these deaths occurred in hospitals (73.6% in 2007 versus 74.8% in 2016). Death rates due to stroke increased from 138 (95% CI 135-142) to 163 (95% CI 159-166) per 100,000 inhabitants. This raise occurred mainly in those over 79 years old. For the ages groups of 34 to 44 and 44 to 54 years, mortality rate decreased. CONCLUSIONS: In the past 15 years, despite the advances in the diagnosis and treatment of stroke, there has been an increase in mortality due to stroke in the state of Paraná. This fact is possibly associated with the aging of the population because there was a more pronounced increase in the group over 79 years old. Thus, new health strategies are necessary to improve the survival and quality of life of poststroke individuals.

ANTECEDENTES: O acidente vascular cerebral (AVC) é a segunda principal causa de morte e invalidez em todo o mundo. OBJETIVO: O objetivo desse estudo é avaliar as taxas de mortalidade específicas por idade e sexo relacionadas ao AVC no estado do Paraná, Brasil, entre 2007 e 2016. MéTODOS: Neste estudo transversal, foram selecionados residentes no estado do Paraná por certidões de óbito (de 2007­2016); a causa básica da morte foi AVC. Uma análise descritiva foi realizada e as taxas de mortalidade calculadas com intervalo de confiança de 95% (IC 95%) para cada ano. RESULTADOS: De 2007 a 2016, ocorreram 62.607 óbitos no estado do Paraná por AVC. A maioria dos indivíduos teve assistência médica antes do óbito (85,7% em 2007 contra 83,9% em 2016), e a maioria desses óbitos ocorreu em hospitais (73,6% em 2007 contra 74,8% em 2016). As taxas de mortalidade por AVC aumentaram de 138 (IC 95% 135­142) para 163 (IC 95% 159­166) por 100.000 habitantes. Esse aumento ocorreu principalmente em maiores de 79 anos. Para as faixas etárias de 34 a 44 e 44 a 54 anos, a taxa de mortalidade diminuiu. CONCLUSõES: Nos últimos 15 anos, apesar dos avanços no diagnóstico e tratamento do AVC, houve aumento da mortalidade no estado do Paraná. Este fato está possivelmente associado ao envelhecimento da população, pois houve um aumento mais acentuado no grupo acima de 79 anos. Assim, novas estratégias de saúde são necessárias para melhorar a sobrevida e a qualidade de vida dos indivíduos pós-AVC.

Environmental Contaminants Modulate Breast Cancer Development and Outcome in TP53 p.R337H Carriers and Noncarriers.

Two major concerns associated with cancer development in Paraná state, South Brazil, are environmental pollution and the germline TP53 p.R337H variant found in 0.27−0.30% of the population. We assessed breast cancer (BC) risk in rural (C1 and C2) and industrialized (C3) subregions, previously classified by geochemistry, agricultural productivity, and population density. C2 presents lower organochloride levels in rivers and lower agricultural outputs than C1, and lower levels of chlorine anions in rivers and lower industrial activities than C3. TP53 p.R337H status was assessed in 4658 women aged >30 years from C1, C2, and C3, subsequent to a genetic screening (Group 1, longitudinal study). BC risk in this group was 4.58 times higher among TP53 p.R337H carriers. BC prevalence and risk were significantly lower in C2 compared to that in C3. Mortality rate and risk associated with BC in women aged >30 years (n = 8181 deceased women; Group 2) were also lower in C2 than those in C3 and C1. These results suggest that environmental factors modulate BC risk and outcome in carriers and noncarriers.

Facial Nerve Adherence in Vestibular Schwannomas: Classification and Radiological Predictors.

Background Facial nerve palsy is one of the most frequent complications after resection of vestibular schwannomas (VS). Several mechanisms have been implicated in the poor postoperative facial nerve outcome. Adherence between the facial nerve and tumor capsule is one of the most relevant factors. There is no clear preoperative parameter permitting identification of these adhesions. Objective The aim of this study was to identify the correlation between the grade of adherence of the facial nerve to the tumor capsule and its functional outcome after VS resection. Methods A total of 26 patients with sporadic VS (tumor sized T3, T4A, and T4B according to Hannover classification) were evaluated. Grade of adherence of the facial nerve to the tumor capsule was checked during surgery and graduated according to a proposed scale into 1 to 3 different grades. Facial nerve function was assessed postoperatively and after 1-year follow-up. Size of tumor according to Hannover classification, presence of cystic components, "cerebrospinal fluid (CSF) cleft sign," and the contour of tumor capsule were tested as radiological predictors of grade of adherence to the facial nerve. Results and Conclusion Only Grade 2 (11 cases) and 3 (15 cases) of adherence were seen in large VS. Lower grade of adherence was associated with good facial nerve outcome after 1-year follow-up ( p = 0.029). Presence of the "CSF cleft sign" and regular contour of tumor capsule were independent predictors of adherence. When both factors were associated, sensitivity and specificity of this method were 83 and 80%, respectively.

Conversion of agricultural waste into stable biocrude using spinel oxide catalysts.

Biomass, the feedstock for biocrude and ultimately renewable diesel is a low energy density feedstock. The transport of this feedstock over long distance has been proven to be a major burden on the commercialisation of biorefining. Therefore, it has been generally accepted that biomass should be upgraded to biocrude (a relatively high energy density liquid) in close proximity to the biomass sources. The biocrude liquid would then be transported to a biorefinery. Biocrude contains large amounts of oxygen (generally up to 38 wt%) that is removed from the crude in the refining process. In this study, we have synthesised a range of spinel oxide based catalysts to remove oxygen from the biocrude during the catalytic fast pyrolysis. The activity of spinel oxide (MgB2O4 where B = Fe, Al, Cr, Ga, La, Y, In) catalysts were screened for the pyrolysis reaction. While all the tested spinel oxides deoxygenated the pyrolysis vapour, MgCr2O4 was found to be effective in terms of oxygen removal efficiency relative to the quantity of bio oil produced.

Anterior Transpetrosal Approach and Microsurgical Resection of a Petrous Tentorial Meningioma: 3-Dimensional Operative Video.

Tentorial meningiomas are challenging tumors because of its complex relationship with vital neurovascular structures. We present the case of a 41-yr-old female with a history of right-sided facial numbness associated with pain around the ear. Magnetic resonance imaging demonstrated a lesion in the right tentorium edge closely related with the porus trigeminus, suggestive of a meningioma. Because of worsening of symptoms the patient underwent surgery for tumor removal. A standard temporo-zygomatic craniotomy was performed, followed by an extradural peeling of the middle fossa; the petrous apex was drilled allowing access to the posterior fossa dura. Dural opening was carried connecting the temporal and posterior fossa, and the tentorium was then cut to the incisura. The tumor was identified and completely removed reaching Simpson grade I resection. Postoperatively, the patient presented a right dry eye in the first days that fully improved, and also a right-sided facial paralysis (House-Brackmann grade IV) and diplopia, both recovered completely after 4 mo. We believe that facial paralysis was the result of an undesired traction of the geniculate ganglion, or upon the nerve itself. To avoid such complication, dissection over the GSPN must be carried parallel to that nerve. Facial numbness and pain improved with no neurological other deficits. Tentorial meningiomas are complex deep-seated lesions that can be successfully approached through an anterior transpetrosal route in selected cases. Informed consent was obtained from the patient for publication of this operative video. Anatomical images were a courtesy of the Rhoton Collection, American Association of Neurological Surgeons/Neurosurgical Research and Education Foundation.

Microsurgical resection of an inferior cerebellar peduncle cavernous malformation: 3-Dimensional operative video.

Brainstem cavernous malformations are especially difficult to treat because of their deep location and intimate relation with eloquent structures. This is the case of a 26-year-old female presenting with dizziness, dysmetria, nystagmus and unbalance. Imaging depicted a lesion highly suggestive of a cavernous malformation in the left inferior cerebellar peduncle. Following a suboccipital midline craniotomy, the cerebellomedullary fissure was dissected and the lesion was identified bulging the surface. The malformation was completely removed with constant intraoperative neurophysiological monitoring. The patient presented improvement of initial symptoms with no new deficits. Surgical resection of brainstem cavernous malformations can be successfully performed, especially when superficial, using the inferior cerebellar peduncle as an entry zone. The video can be found here: https://youtu.be/-GGZe_CaZnQ.

Stroke-related mortality analysis in Paraná, Brazil, over 10 years / Análise da mortalidade relacionada ao acidente vascular cerebral no estado do Paraná, Brasil, ao longo de 10 anos

Abstract Background Stroke is the second leading cause of death and disability around the world. Objective The purpose of this study is to evaluate the age- and sex-specific mortality rates related to stroke in the state of Paraná, Brazil, between 2007 and 2016. Methods In this cross-sectional study, residents in the state of Paraná were selected by death certificates (from 2007-2016); the basic cause of death was stroke. A descriptive analysis was performed, and mortality rates were calculated with a 95% confidence interval (95% CI) for each year. Results From 2007 to 2016, there were 62,607 deaths in the state of Paraná due to stroke. Most individuals had medical assistance before death (85.7% in 2007 versus 83.9% in 2016), and most of these deaths occurred in hospitals (73.6% in 2007 versus 74.8% in 2016). Death rates due to stroke increased from 138 (95% CI 135-142) to 163 (95% CI 159-166) per 100,000 inhabitants. This raise occurred mainly in those over 79 years old. For the ages groups of 34 to 44 and 44 to 54 years, mortality rate decreased. Conclusions In the past 15 years, despite the advances in the diagnosis and treatment of stroke, there has been an increase in mortality due to stroke in the state of Paraná. This fact is possibly associated with the aging of the population because there was a more pronounced increase in the group over 79 years old. Thus, new health strategies are necessary to improve the survival and quality of life of poststroke individuals.

Resumo Antecedentes O acidente vascular cerebral (AVC) é a segunda principal causa de morte e invalidez em todo o mundo. Objetivo O objetivo desse estudo é avaliar as taxas de mortalidade específicas por idade e sexo relacionadas ao AVC no estado do Paraná, Brasil, entre 2007 e 2016. Métodos Neste estudo transversal, foram selecionados residentes no estado do Paraná por certidões de óbito (de 2007-2016); a causa básica da morte foi AVC. Uma análise descritiva foi realizada e as taxas de mortalidade calculadas com intervalo de confiança de 95% (IC 95%) para cada ano. Resultados De 2007 a 2016, ocorreram 62.607 óbitos no estado do Paraná por AVC. A maioria dos indivíduos teve assistência médica antes do óbito (85,7% em 2007 contra 83,9% em 2016), e a maioria desses óbitos ocorreu em hospitais (73,6% em 2007 contra 74,8% em 2016). As taxas de mortalidade por AVC aumentaram de 138 (IC 95% 135-142) para 163 (IC 95% 159-166) por 100.000 habitantes. Esse aumento ocorreu principalmente em maiores de 79 anos. Para as faixas etárias de 34 a 44 e 44 a 54 anos, a taxa de mortalidade diminuiu. Conclusões Nos últimos 15 anos, apesar dos avanços no diagnóstico e tratamento do AVC, houve aumento da mortalidade no estado do Paraná. Este fato está possivelmente associado ao envelhecimento da população, pois houve um aumento mais acentuado no grupo acima de 79 anos. Assim, novas estratégias de saúde são necessárias para melhorar a sobrevida e a qualidade de vida dos indivíduos pós-AVC.