Onset and duration of symptoms of loss of smell/taste in patients with COVID-19: A systematic review.

OBJECTIVE: The aim of the study was to conduct a systematic review of the literature to investigate the time of onset and duration of symptoms of loss of smell and taste in patients diagnosed with COVID-19. METHODS: Two independent authors performed a systematic review of the Medline/PubMed, SCOPUS, COCHRANE, Lilacs and Web of Science electronic databases. The time of onset and duration of symptoms were considered primary outcomes. The sex and age of individuals, the geographical location of the study, the prevalence of symptoms, other associated symptoms, associated comorbidities, and the impact on quality of life and eating habits were considered secondary outcomes. RESULTS: Our search generated 17 articles. Many of the studies reported that the onset of anosmia and ageusia occurred 4 to 5 days after the manifestation of other symptoms of the infection and that these symptoms started to disappear after one week, with more significant improvements in the first two weeks. CONCLUSION: The present study concludes that the onset of symptoms of loss of smell and taste, associated with COVID-19, occurs 4 to 5 days after other symptoms, and that these symptoms last from 7 to 14 days. Findings, however, varied and there is therefore a need for further studies to clarify the occurrence of these symptoms. This would help to provide early diagnosis and reduce contagion by the virus.

Peripheral and Central Glucocorticoid Signaling Contributes to Positive Energy Balance in Rats.

The obesity epidemic has been the target of several studies to understand its etiology. The pathophysiological processes that take to obesity generally relate to the rupture of energy balance. This imbalance can result from environmental and/or endogenous events. Among the endogenous events, the hypothalamic-pituitary-adrenal axis, which promotes stress response via glucocorticoid activity, is considered a modulator of energy balance. However, it remains controversial whether the increase in plasma levels of glucocorticoids results in a positive or negative energy balance. Furthermore, there are no studies comparing different routes of administration of glucocorticoids in this context. Here, we investigated the effects of intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of a specific agonist for glucocorticoid receptors on food intake and energy expenditure in rats. Sixty-day old rats were treated with i.p. or i.c.v. dexamethasone. Food intake and satiety were evaluated, as well as locomotor activity in order to determine energy expenditure. Both i.p. and i.c.v. dexamethasone increased food intake and decreased energy expenditure. Moreover, i.c.v. dexamethasone delayed the onset of satiety. Together, these results confirm that central glucocorticoid signaling promotes a positive energy balance and supports the role of the glucocorticoid system as the underlying cause of psychological stress-induced obesity.

Social isolation and post-weaning environmental enrichment effects on rat emotional behavior and serotonergic system.

Social isolation (SI) is related to adverse neurobehavioral effects and neurochemical changes when it occurs early in development. On the other hand, environmental enrichment (EE) is associated with a reduction in anxiety-like and depression-like behavior, as well as an increase in serotonin (5-HT) levels in the prefrontal cortex and hippocampus in rodents. This study systematically reviewed the effects of SI and EE on emotional behavior and serotonergic system components in rats after weaning. Primary experimental studies that used subgroups of rats subjected to SI, EE, and normal social conditions after weaning were considered eligible. Studies that used transgenic rodents, ex vivo studies, in vitro studies, human research, or in silico studies were ineligible. Two authors completed searches in Medline/PubMed, LILACS, Scopus, Web of Science, EMBASE, and Open Gray. The Kappa index was calculated to assess agreement between reviewers and assess study quality. The results showed that the animals exposed to EE showed better adaptation to a new environment. Furthermore, EE increased 5-HT levels in the hippocampus and prefrontal cortex of rodents. Thus, it appears that an EE during the critical period of development may reduce anxiety/depression-like behaviors, as well as increase long-term neurotransmitter response.

Cardiovascular and Renal Effects Induced by Alpha-Lipoic Acid Treatment in Two-Kidney-One-Clip Hypertensive Rats.

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.

Effects of maternal high-fat diet on the hypothalamic components related to food intake and energy expenditure in mice offspring.

Maternal exposure to a high-fat diet (HFD) during pregnancy and lactation has been related to changes in the hypothalamic circuits involved in the regulation of food intake. Furthermore, maternal HFD during the critical period of development can alter the offspring's metabolic programming with long-term repercussions. This study systematically reviewed the effects of HFD consumption during pre-pregnancy, pregnancy and/or lactation. The main outcomes evaluated were food intake, body weight and cellular or molecular aspects of peptides and hypothalamic receptors involved in the regulation of energy balance in mice. Two independent authors performed a search in the electronic databases Medline/PubMed, LILACS, Web of Science, EMBASE, SCOPUS and Sigle via Open Gray. The experimental studies of mice exposed to HFD during pregnancy and/or lactation that evaluated body composition, food intake, energy expenditure and hypothalamic components related to energy balance were included. Internal validity was assessed using the SYRCLE risk of bias. The Kappa index was measured to analyze the agreement between reviewers. The PRISMA statement was used to report this systematic review. Most studies demonstrated that there was a higher body weight, body fat deposits and food intake, as well as alterations in the expression of hypothalamic neuropeptides in offspring that consumed HFD. Therefore, the maternal diet can affect the phenotype and metabolism of the offspring, in addition to harming the hypothalamic circuits and favoring the orexigenic pathways.

Effects of flavonols on emotional behavior and compounds of the serotonergic system: A preclinical systematic review.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that regulates multiple psychophysiological functions. An imbalance of 5-HT in the brain can modulate emotional behavior such as depression and anxiety. Substances, such as flavonols, naturally found in some plants and foods have beneficial effects on psychiatric disorders, have been studied. The aim of this systematic review was to investigate the effects of flavonols on morphological, physiological, and cellular aspects of the serotonergic system as well as on some behaviors modulated by this system. Literature searches were performed in the LILACS, Web of Science, Scopus, PubMed and Sigle via Open Grey databases, from which 1725 studies were found. Using a predefined protocol registered on the CAMARADES website, 18 studies were chosen for qualitative synthesis. Internal validity was assessed using the SYRCLE's risk of bias tool. The Kappa index was also measured to analyze agreement among the reviewers. The results of this systematic review showed that flavonols have been reported to modify physiological aspects of the serotonergic system, increasing levels of serotonin and decreasing levels of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and promoting antioxidant effects in encephalic regions. Moreover, the results showed that flavonols can also modulate of the serotonergic system, being associated with antidepressant and anxiolytic activities. Additionally, flavonols were found to not have psychostimulant effect; they can, however, reverse damage to locomotor activity.

Maternal exposure to high-fat diet modifies anxiety-like/depression-like behaviors and compounds of Serotonergic System in offspring: A preclinical systematic review.

Maternal nutrition affects offspring physiology and behavior including susceptibility to mental health-related states. Perinatal high-fat diet (HFD) consumption has been associated with lower levels of serotonin as well as the development of anxiety-like and depression-like behaviors in offspring. The aim of this systematic review was to investigate the effects of maternal HFD during pregnancy and/or lactation on these behaviors and on some aspects of the serotonergic system. Criteria for eligibility included studies of offspring of rodents and non-human primates exposed to HFD at least during pregnancy and/or lactation, offspring that showed outcomes related to anxiety-like and depression-like behaviors and to the serotonergic system. The searches were realized in the LILACS, Web of Science, Scopus, and PubMed databases. The systematic review protocol was registered on the CAMARADES website. The internal validity was assessed by the SYRCLE risk of bias tool. The Kappa index was used for analyzing agreement among the reviewers. In addition, the PRISMA statement was used to report this systematic review. Sixteen articles were included in this review. Most of which studied HFD prior to mating and during pregnancy and lactation. All studies analyzed outcomes related to emotional behavior; three analyzed outcomes related to serotonin system compounds. Maternal consumption of HFD was found to be associated with an inconsistent pattern of the expression of TPH2 as well as reduced the immunoreactivity of 5-HT in the prefrontal cortex and increased 5-HT1A receptor expression in the dorsal raphe of offspring. An association between an HFD and alterations in emotional behavior was found in most of the studies selected.

Neonatal fluoxetine exposure modulates serotonergic neurotransmission and disturb inhibitory action of serotonin on food intake.

The neurotransmitter serotonin (5-HT) acts as an important regulator of the critical neurodevelopmental processes and thus alterations in 5-HT signaling early promotes permanent structural and functional changes in brain. The selective serotonin reuptake inhibitors (SSRIs), as fluoxetine and citalopram, blocking serotonin transporter (SERT) at the presynaptic neuron, which regulates extracellular 5-HT levels. Evidence suggests that the exposure to SSRIs in the neurodevelopmental period may alters 5-HT signaling sensitivity on food intake control. The aim of the present study was to evaluate the effects of neonatal exposure to fluoxetine on molecular and cellular components of the serotonergic system and food intake control in young animals. Methods: The animals were divided according to experimental manipulation, Fluoxetine Group (FG): male pups received application of fluoxetine (10 mg/kg, 10 µL/g) and Saline Group (SG): male pups received saline application (0.9% NaCl, 10 µL/g), both throughout lactation (PND1-PND21). They evaluated body weight, food intake, SERT gene and protein expression, serotonin content in the hypothalamus. The neonatal exposure to fluoxetine promoted reduction in body weight, disturb the serotonin hypophagic response, and increase the serotonin and SERT hypothalamic in young animals. We conclude that the changes of components of the serotonergic system by neonatal exposure to fluoxetine may be responsible for disturb the inhibitory action of serotonin on food intake.

Effects of maternal low-protein diet on parameters of locomotor activity in a rat model of cerebral palsy.

Children with cerebral palsy have feeding difficulties that can contribute to undernutrition. The aim of this study was to investigate the effect of early undernutrition on locomotor activity and the expression of the myofibrillar protein MuRF-1 in an experimental model of cerebral palsy (CP). In order to achieve this aim, pregnant rats were divided into two groups according to the diet provided: Normal Protein (NP, n=9) and Low Protein (LP, n=12) groups. After birth, the pups were divided into four groups: Normal Protein Sham (NPS, n=16), Normal Protein Cerebral Palsy (NPCP, n=21), Low Protein Sham (LPS, n=20) and Low Protein Cerebral Palsy (LPCP, n=18) groups. The experimental cerebral palsy protocol consisted of two episodes of anoxia at birth and during the first days of life. Each day, nitrogen flow was used (9l/min during 12min). After nitrogen exposure, sensorimotor restriction was performed 16h per day, from the 2nd to the 28th postnatal day (PND). Locomotor activity was evaluated at 8th, 14th, 17th, 21th and 28th PND. At PND 29, soleus muscles were collected to analyse myofibrillar protein MuRF-1. Our results show that CP animals decreased body weight (p<0.001), which were associated with alterations of various parameters of locomotor activity (p<0.05), compared to their control. Undernourished animals also showed a decrease (p<0.05) in body weight and locomotor activity parameters. Moreover, CP decreased MuRF-1 levels in nourished rats (p=0.015) but not in undernourished rats. In summary, perinatal undernutrition exacerbated the negative effects of cerebral palsy on locomotor activity and muscle atrophy, but it appears not be mediated by changes in MuRF-1 levels.

[Effect of physical training on the bone tissue and the calcium serum concentration in ovariectomized mice]. / Efeito do treinamento físico sobre o tecido ósseo e a concentração sérica de cálcio em camundongos fêmeas ovariectomizadas.

PURPOSE: The aim of this study is to evaluate possible morphometric alterations in bone tissue and the calcium serum concentration in ovariectomized mice subjected to physical training. METHODS: Fifty female mice, aged 90 days, divided into 5 groups (n=10): control (C), pseudo-operated sedentary (POS), pseudo-operated trained (POT), ovariectomized sedentary (OVS) and ovariectomized trained (OVT). Groups OVS and OVT were subjected to an ovariectomy, and groups POS and POT were subjected to a pseudo-surgery. Thirty days after the surgery, groups POT and OVT were subjected to physical training during 05 weeks in ergometer at a speed of 20 m/min. The other animals stayed sedentary at the same period. Afterwards the animals were sacrificed and had blood collected to realize calcium serum dosage and the right femurs were collected to realize a histomorphometric study. RESULTS: The calcium serum concentration in group OVT was lower than the other groups (p<0.05). The mass of femurs in groups POT and OVT was higher than the group Control (p<0.05). The average density of the osteocytes was higher in group OVS (p<0.05). The average value of the area of the osteocytes showed difference only between groups POS and OVS (p<0.05). There were no differences in the bone length, nor in the osteocytes perimeter. CONCLUSION: The physical training in part prevented the alterations in the bone tissue due to the ovariectomy and enabled an increase of the bone formation.

Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats.

BACKGROUND: Serotonin (5-HT) is involved in nervous system ontogenesis, and is important for neurotransmission and behavior modulation after the developmental stage. Alterations in 5-HT levels during the early period of life may signal to feeding behavior and hypothalamic genic expression changes in adulthood. OBJECTIVES: Investigate the effects of hypercaloric diet in adult rats submitted to neonatal serotonin reuptake inhibition on food intake, fat pad mass, plasmatic triglycerides/cholesterol and gene expression of hypothalamic peptides (POMC, NPY) and serotonin receptors (5-HT1B, 5-HT2C). METHODS: In each litter, 8 pups were divided into two groups: control (C) and fluoxetine (F). From the 1(st) to the 21(st) postnatal day, C pups received sterile saline while F pups received fluoxetine (10mg/kg). From 180 to 215 days, a group of rats from C and F groups were fed hypercaloric diet (CH and FH, 421.4Kcal/100 g) while the rest of animals from C and F groups fed chow diet (CC and FC). RESULTS: The use of hypercaloric diet was associated with lower accumulation of white adipose tissue in adult rats subjected to neonatal serotonin reuptake inhibition. Adult rats of group FC showed decreased 5-HT2C and neuropeptide Y mRNA expression compared with control chow diet group (CC). After chronic use of a hypercaloric diet, the expression of 5-HT2C was higher in the FH group than the FC group and neuropeptide Y expression decreased in FH related to FC. CONCLUSIONS: These findings suggest that neonatal serotonin reuptake inhibition is associated with better adaptation to hypercaloric diet in adult rats.

Perinatal serotonergic activity: A decisive factor in the control of food intake / Atividade serotoninérgica perinatal: um fator decisivo para o controle da ingestão alimentar

ABSTRACT The serotoninergic system controls key events related to proper nervous system development. The neurotransmitter serotonin and the serotonin transporter are critical for this control. Availability of these components is minutely regulated during the development period, and the environment may affect their action on the nervous system. Environmental factors such as undernutrition and selective serotonin reuptake inhibitors may increase the availability of serotonin in the synaptic cleft and change its anorectic action. The physiological responses promoted by serotonin on intake control decrease when requested by acute stimuli or stress, demonstrating that animals or individuals develop adaptations in response to the environmental insults they experience during the development period. Diseases, such as anxiety and obesity, appear to be associated with the body's response to stress or stimulus, and require greater serotonergic system action. These findings demonstrate the importance of the level of serotonin in the perinatal period to the development of molecular and morphological aspects of food intake control, and its decisive role in understanding the possible environmental factors that cause diseases in adulthood.

RESUMO O sistema serotoninérgico apresenta funções no controle de eventos biológicos fundamentais para o desenvolvimento adequado do sistema nervoso. A serotonina e o transportador de serotonina são indispensáveis para esta função de controle. A disponibilidade destes componentes é precisamente regulada durante o período de desenvolvimento, e podem sofrer interferências provindas do ambiente alterando sua ação sobre o sistema nervoso. A desnutrição, a inibição da recaptação da serotonina a partir de fármacos e mudanças na expressão de gênica do transportador de serotonina na gestação e lactação podem induzir o aumento de serotonina alterando sua ação anorexígena. As respostas fisiológicas desempenhadas pela serotonina no controle da ingestão exibem uma resistência quando requisitadas por estímulos ou estresses agudos, demonstrando que os animais ou indivíduos desenvolvem adaptações de acordo com as agressões ambientais sofridas no período de desenvolvimento. Patologias como, ansiedade e obesidade, parecem estar associadas à resposta do organismo a um estresse ou estímulo, necessitando de uma maior ação do sistema serotoninérgico. Estes achados demonstram a importância do conteúdo da serotonina no período perinatal ao desenvolvimento de aspectos moleculares e morfológicos do controle da ingestão alimentar, e sua função determinante para a compreensão das possíveis influências ambientais causadoras de patologias na vida adulta.

Perinatal stress: characteristics and effects on adult eating behavior / Estresse peri-natal: suas características e repercussões sobre o comportamento alimentar na vida adulta

Many studies have pointed out the importance of mother-child interaction in the early months of life. A few decades ago, a method called kangaroo care was developed and its main goal was to keep underweight or premature newborns in direct contact with the mother. This method has reduced the morbidity and mortality of these newborns, increasing their growth rate, breastfeeding time and mother-child contact. In rodents, the dam's presence is crucial for avoiding aggression factors that may trigger phenotypic adaptations in the pups with irreversible morphological, functional and behavioral consequences. Eating behavior is an adaptive response stemming from the external environment demand and modulated by opportunities and limitations imposed by the external environment. This behavior is regulated by a complex interaction of peripheral and central mechanisms that control hunger and satiety. The hypothalamus is a brain structure that integrates central and peripheral signals to regulate energy homeostasis and body weight. The hypothalamic nucleus have orexigenic peptides, such as neuropeptide Y and the Agouti-related peptide, and anorexigenic peptides, such as cocaine and amphetamine regulated transcript and proopiomelanocortin. An innovative study of eating behavior in experimental models of neonatal stress separates the mother from the offspring during lactation. This review describes the effects of stress during the neonatal period on general physiological factors, particularly on the control of eating behavior.

Muitos estudos têm apontado a importância da interação mãe-filho durante os primeiros meses de vida. Nas últimas décadas, foi desenvolvido um método, denominado mãe canguru, que tem como principal objetivo manter neonatos nascidos com baixo peso ou prematuros em contato direto com suas mães de forma contínua. Esse método tem reduzido a mortalidade e morbidade desses neonatos, aumentado medidas de crescimento, amamentação e contato mãe-filho. Em roedores, a presença da mãe é determinante para evitar a incidência de fatores agressores que possam desencadear adaptações fenotípicas dos filhotes com consequências morfofuncionais e comportamentais irreversíveis. O comportamento alimentar representa uma resposta adaptativa, decorrente da demanda do ambiente interno sendo modulado por oportunidades e limitações impostas pelo ambiente externo.Esse comportamento é regulado por uma interação complexa entre mecanismos periféricos e centrais que controlam a fome e a saciedade. O hipotálamo é a estrutura encefálica que integra sinais centrais e periféricos para regular a homeostase energética e o peso corporal. Nos núcleos hipotalâmicos são encontrados peptídeos orexigênicos como o neuropeptídeo Y e o peptídeo relacionado ao gene Agouti, e os anorexigênicos como o transcrito relacionado a cocaína e anfetamina e a pró-opiomelanocortina. O estudo do comportamento alimentar é inovador em modelos experimentais de estresse neonatal utilizando a separação entre mães e filhotes na fase de lactação. Esta revisão descreve os efeitos do estresse durante o período neonatal sobre aspectos fisiológicos gerais e particularmente sobre o controle do comportamento alimentar.

Efeito do treinamento físico sobre o tecido ósseo e a concentracão sérica de cálcio em camundongos fêmeas ovariectomizadas / Effect of physical training on the bone tissue and the calcium serum concentration in ovariectomized mice

OBJETIVO: Investigar as possíveis alteracões morfométricas no tecido ósseo e na concentracão sérica de cálcio em camundongos ovariectomizadas submetidas ao treinamento físico. MÉTODOS: Cinqüenta camundongos fêmeas, com 90 dias de idade, distribuídos em 5 grupos (n=10): controle (C), pseudo-operado sedentário (POS), pseudo-operado treinado (POT), ovariectomizado sedentário (OVS) e ovariectomizado treinado (OVT). Os grupos OVS e OVT foram submetidos a ovariectomia, e os grupos POS e POT a uma pseudo-cirurgia. Trinta dias após a cirurgia, os grupos POT e OVT foram submetidos ao exercício físico, durante 05 semanas em esteira elétrica a uma velocidade de 20 m/min. Os demais animais permaneceram sedentários no mesmo período. Após esse período os animais foram sacrificados, coletando o sangue para realizacão de dosagens séricas de cálcio e os fêmures direitos para estudo histomorfométrico. RESULTADOS: A concentracão sérica de cálcio no grupo OVT apresentou-se mais baixa do que nos demais grupos (p<0,05). A massa dos fêmures mostrou-se superior em relacão ao grupo controle, nos grupos POT e OVT (p<0,05). A densidade média de osteócitos foi mais alta no grupo OVS (p<0,05). O valor médio da área dos osteócitos mostrou diferenca apenas entre os grupos POS e OVS (p<0,05). Não houve diferencas no comprimento ósseo nem no perímetro dos osteócitos. CONCLUSAO: O exercício, em parte, preveniu as alteracões do tecido ósseo decorrentes da ovariectomia e possibilitou um aumento da formacão óssea.

An anthropometric radiographic study of the intercondylar notch in brazilian males and females

The anthropometric aspects of the femoral intercondylar notch and the femoral condyles in knees of male and female young adult individuals were analyzed at this study. Forty-six simple X-rays of the femoral intercondylar notch of right and left knees taken from 46 (18 to 35 year-old individuals), without manifestation of any pathological condition of the lower limbs. The individuals were divided into group G1 with: 23 knee of male individuals and group G1 with 23 knee of female individuals. The radiographic images were digitalized through a scanner. The comparative analysis showed that the values of femoral bicondylar width, femoral intercondylar notch base width, femoral intercondylar notch apex width, lateral and medial femoral condyle widths were greater on males. The opening femoral intercondylar notch angle showed greater values in male sex individuals while the Intercondyle Width Index (I.W.I.), expressed through the relation between the notch´s width and the femoral bicondylar width at the popliteal´s wrinkle level and whose value can be used as prediction to anterior cruciate ligament (ACL) injuries, showed greater values in female sex individuals. The values of height and width of femoral intercondylar notch did not show differences between the sexes. Our results suggest that females have greater predisposition to ACL injury.