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Disturbed sleep is common in asthma. Melatonin has sleep-inducing activity and reportedly affects smooth muscle tone and inflammation. The aim of this study was to evaluate the effect of melatonin on sleep in patients with mild and moderate asthma. This was a randomized, double-blind, placebo-controlled study. Twenty-two consecutive women with asthma were randomized to receive melatonin 3 mg (n = 12) or placebo (n = 10) for 4 weeks. Sleep quality and daytime somnolence were assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, respectively. Pulmonary function was assessed by spirometry. Use of relief medication, asthma symptoms, and morning and evening peak expiratory flow rate were recorded daily. Melatonin treatment significantly improved subjective sleep quality, as compared with placebo (p = 0.04). No significant difference in asthma symptoms, use of relief medication and daily peak expiratory flow rate was found between groups. We conclude that melatonin can improve sleep in patients with asthma. Further studies looking into long-term effects of melatonin on airway inflammation and bronchial hyperresponsiveness are needed before melatonin can be recommended in patients with asthma. [ABSTRACT FROM AUTHOR]

This study mapped definitions of shortened dental configurations and health outcomes employed in association studies. A scoping review was conducted using the PubMed/Medline, Scopus, Web of Science, SciELO and Cochrane databases. Two trained researchers selected studies and extracted data. Studies that investigated the association between shortened dental configurations (exposure) and person-centered outcomes (general and oral health) related to health behavior (dietary patterns). Clinical outcomes were classified according to the International Classification of Functioning, Disability and Health and the International Classification of Diseases of the World Health Organization (WHO). Shortened dental configurations were defined as at least 20/21 teeth or the position of the teeth, including esthetics, dental occlusion and periodontal status (Eichner Index, Shortened Dental Arches, Functional Dentition Classification System, Posterior Occluding Pairs, Functional Tooth Units). The initial search resulted in 12,525 records in English, Portuguese and Spanish, 432 of which addressed the association of interest. General health (n = 203) and oral health (n = 201) were addressed in a similar number of studies. Most outcomes were related to general health (n = 184), the most frequent of which were endocrine, nutritional or metabolic diseases (n = 57) and mental functions (n = 26). Person-centered measures were addressed in 153 studies, most of which were about oral health and oral health-related quality of life (n = 62). Oral health outcomes were predominantly related to intake functions (n = 44) and diseases or disorders of the orofacial complex (n = 24). Dietary patterns (n = 43) and mortality (n = 38) were also studied. The cross-sectional design (n = 257) and non-probabilistic sampling (n = 218) were more frequent. The shortened dental configurations defined by the WHO were the most frequent in the studies (n = 206). The effects of shortened dental configurations have been investigated mainly in relation to endocrine, nutritional or metabolic diseases and measures of oral health-related quality of life. The findings point to a diversity of health outcomes assessed and substantial methodological variability., (© 2024. The Author(s).)

Overactivation of microglial cells seems to play a crucial role in the degeneration of dopaminergic neurons occurring in Parkinson's disease. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) present in astrocytes secretome modulates microglial responses induced by an inflammatory insult. Therefore, astrocyte-derived soluble factors may include relevant molecular players of therapeutic interest in the control of excessive neuroinflammatory responses. However, in vivo, the control of neuroinflammation is more complex as it depends on the interaction between different types of cells other than microglia and astrocytes. Whether neurons may interfere in the astrocyte-microglia crosstalk, affecting the control of microglial reactivity exerted by astrocytes, is unclear. Therefore, the present work aimed to disclose if the control of microglial responses mediated by astrocyte-derived factors, including GDNF, could be affected by the crosstalk with neurons, impacting GDNF's ability to protect dopaminergic neurons exposed to a pro-inflammatory environment. Also, we aimed to disclose if the protection of dopaminergic neurons by GDNF involves the modulation of microglial cells. Our results show that the neuroprotective effect of GDNF was mediated, at least in part, by a direct action on microglial cells through the GDNF family receptor α-1. However, this protective effect seems to be impaired by other mediators released in response to the neuron-astrocyte crosstalk since neuron-astrocyte secretome, in contrast to astrocytes secretome, was unable to protect dopaminergic neurons from the injury triggered by lipopolysaccharide-activated microglia. Supplementation with exogenous GDNF was needed to afford protection of dopaminergic neurons exposed to the inflammatory environment. In conclusion, our results revealed that dopaminergic protective effects promoted by GDNF involve the control of microglial reactivity. However, endogenous GDNF is insufficient to confer dopaminergic neuron protection against an inflammatory insult. This reinforces the importance of further developing new therapeutic strategies aiming at providing GDNF or enhancing its expression in the brain regions affected by Parkinson's disease.

Locally advanced rectal cancer has traditionally been treated with chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, a new strategy, total neoadjuvant therapy, involves the administration of CRT and neoadjuvant chemotherapy with the aim of eradicating micrometastases earlier and achieving greater control of the disease. The use of total neoadjuvant therapy has shown higher rates of pathological complete response and resectability compared with CRT, including improved survival. Nevertheless, distant relapse is the main cause of morbidity and mortality in locally advanced rectal cancer. To address this, new biomarkers are being developed to predict disease response.

The aim of this study was to evaluate the accuracy of pairs of antagonist teeth (epidemiological criterion) for defining pairs of teeth in occlusal contact (clinical criterion) and to estimate the agreement between the prevalence of "shortened dental arch" (SDA) and "functional dentition" (FD) when occlusal units (OUs) or posterior occluding pairs (POPs) are defined by the epidemiological or clinical criterion. Data were collected in an epidemiological oral health survey conducted in a municipality in Minas Gerais, Brazil. OUs and POPs were defined by the epidemiological criterion (dental crown status) or clinical criterion "gold standard" (carbon paper record of occlusal contacts during habitual maximum intercuspation). SDA corresponded to the presence of an intact anterior region and three to five OUs. FD was based on the concomitant presence of ≥ 1 tooth in each arch, 10 teeth in each arch, 12 anterior teeth, ≥ 3 premolar POPs, and ≥ 1 molar POP bilaterally. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the epidemiological criterion were calculated. The study included 197 adults. Sensitivity, specificity, PPV, and NPV were 88.5, 87.9, 92.5, and 81.9%, respectively, and accuracy was 88.3%. The epidemiological criterion proved to be valid and could be used in epidemiological studies to calculate the prevalence of reduced dental configurations that consider POPs. The assessment of oral functionality is an aspect that should be included in the diagnosis of the clinical condition of patients, contributing to a more effective individual and collective oral health care plan.

Colorectal cancer has been considered a worldwide public health problem since current treatments are often ineffective. Irinotecan is a frontline chemotherapeutic agent that has dose-limiting side effects that compromise its therapeutic potential. Therefore, it is necessary to develop a novel, targeted drug delivery system with high therapeutic efficacy and an improved safety profile. Here, micellar formulations composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG 2k ) containing irinotecan were proposed as a strategy for colorectal cancer therapy. Firstly, the irinotecan-loaded micelles were prepared using the solvent evaporation method. Then, micelles were characterized in terms of size, polydispersity, zeta potential, entrapment efficiency, and release kinetics. Cytotoxicity and in vivo antitumor activity were evaluated. The micelles showed size around 13 nm, zeta potential near neutral (-0.5 mV), and encapsulation efficiency around 68.5% (irinotecan 3 mg/mL) with a sustained drug release within the first 8 h. The micelles were evaluated in a CT26 tumor animal model showing inhibition of tumor growth (89%) higher than free drug (68.7%). Body weight variation, hemolytic activity, hematological, and biochemical data showed that, at the dose of 7.5 mg/kg, the irinotecan-loaded micelles have low toxicity. In summary, our findings provide evidence that DSPE-mPEG 2k micelles could be considered potential carriers for future irinotecan delivery and their possible therapeutic application against colorectal cancer.

Background: Socioeconomic inequalities in tooth loss might be minimized or potentialized by the characteristics of the context where people live. We examined whether there is contextual variation in socioeconomic inequalities in tooth loss across Brazilian municipalities., Methods: Data from the 2010 National Oral Health Survey of 9633 adults living in 157 Brazilian municipalities were used. The individual socioeconomic indicators were education and household income. At the municipal level, we used the Municipal Human Development Index (HDI) as our contextual indicator of socioeconomic status (low:< 0.699 versus high: > 0.70). The Relative (RII) and Slope (SII) Indexes of Inequality, Relative (RCI), and Absolute (ACI) Concentration Indexes were calculated to compare the magnitude of education and income-based inequalities among municipalities with low versus high HDI. Multilevel Poisson regression models with random intercepts and slopes were developed., Results: At the individual level, adults with lower education & income reported more tooth loss. The mean number of missing teeth was 9.52 (95% CI: 7.93-11.13) and 6.95 (95% CI: 6.43-7.49) in municipalities with low and high HDI, respectively. Municipalities with high HDI showed higher relative and absolute education-based inequality. For income-based inequalities, higher SII and RCI was observed in municipalities with lower HDI. A significant cross-level interaction indicated that high-education adults reported fewer missing teeth when they lived in municipalities with high HDI compared to adults with the same education level living in low HDI municipalities. For individuals with the lowest education level, there was no difference in the number of teeth between those from municipalities with high and low HDI., Conclusions: There was a social gradient in tooth loss by education and income. Living in disadvantaged municipalities cannot overcome the risk associated with low schooling. The protective effect of higher education can be reduced when people live in disadvantaged areas.

This study aimed to map evidence-based guidelines for oral care of the dependent elders and perform the cross-cultural adaptation to Brazilian Portuguese. Initially, a systematized review was conducted in Medline, Scielo, Scopus, Web of Science, and Google Scholar databases without restrictions in search period or type of study. Articles in English, Spanish, and Brazilian Portuguese describing evidence-based guidelines for oral care, including oral hygiene recommendations, of institutionalized dependent elders were included as long as they presented an evaluation of evident quality. The guideline that met inclusion criteria was submitted to cross-cultural adaptation after obtaining permission from the original authors. Two hundred and nineteen references were found. Three selected articles described evidence-based guidelines for oral care, but the Oral Health Care Guideline for Older People in Long-term Care Institutions (OGOLI), originally developed and implemented in the Netherlands, was selected. It was based on evidence level A2 and consensus of experts and met the quality requirements of the Appraisal of Guidelines for Research & Evaluation (AGREE). This guideline presents oral care recommendations for elders with different levels of dependence in activities of daily living to be performed by caregivers and nursing staff. The adaptation of the OGOLI was mainly on the attributions of care providers, given the differences in professional regulations between Brazil and the Netherlands. The cross-cultural equivalence between OGOLI and its Brazilian Portuguese version was verified.

Background: Oral health-related quality of life (OHRQoL) has important implications for the clinical practice of dentistry and dental research and should contribute to professional judgment about restorative treatments and prosthetic replacement in patients who had reduced dentitions. The aim was to compare the OHRQoL among adults (35-44 years) categorized according to different definitions of reduced dentition and considering the use (or non-use) of dental prosthesis., Methods: This study used data from a probabilistic sample of adults in Sao Paulo, Brazil, 2015. OHRQoL was based on none items of Oral Impacts on Daily Performance (OIDP) index, as prevalence (at least one impact) and extent (the number of items with non-zero score). We used different criteria to assess dentition status: (1) Shortened Dental Arch (SDA): having 3-5 natural occlusal units (OUs) in posterior teeth and intact anterior region; (2) hierarchical functional classification system: a five-level stepwise classification of dentition; and (3) presence of ≥21 teeth. The use or nonuse of dental prosthesis was recorded. Negative binomial regression models involved the adjustment for social determinants of health., Results: Nearly half (53.1%) of the 5753 participating adults had at least one oral health issue impacting OHRQoL. OIDP prevalence in adults with SDA did not differ from those with more OUs (PR = 1.02; 95%CI 0.91-1.13). Individuals with non-functional dentition had worse OHRQoL regardless of their use of a dental prosthesis. Adults with fewer than 21 remaining teeth, ranked significantly higher in OIDP extent, regardless of dental prosthesis use (PR = 1.38; 95%CI 1.16-1.63 with prosthesis; PR = 1.62; 95%CI 1.19-2.20 without dental prosthesis)., Conclusions: Individuals with more missing teeth reported worse OHRQoL regardless of using a dental prosthesis. Preserving a functional dentition, even with missing teeth, is compatible with OHRQoL.

The use of dopamine replacement therapies (DRT) in the treatment of Parkinson's disease (PD) can lead to the development of dopamine dysregulation syndrome (DDS) and impulse control disorders (ICD), behavioral disturbances characterized by compulsive DRT self-medication and development of impulsive behaviors. However, the mechanisms behind these disturbances are poorly understood. In animal models of PD, the assessment of the rewarding properties of levodopa (LD), one of the most common drugs used in PD, has produced conflicting results, and its ability to promote increased impulsivity is still understudied. Moreover, it is unclear whether acute and chronic LD therapy differently affects reward and impulsivity. In this study we aimed at assessing, in an animal model of PD with bilateral mesostriatal and mesocorticolimbic degeneration, the behavioral effects of LD therapy regarding reward and impulsivity. Animals with either sham or 6-hydroxydopamine (6-OHDA)-induced bilateral lesions in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were exposed to acute and chronic LD treatment. We used the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of LD, whereas impulsive behavior was measured with the variable delay-to-signal (VDS) task. Correlation analyses between behavioral measurements of reward or impulsivity and lesion extent in SNc/VTA were performed to pinpoint possible anatomical links of LD-induced behavioral changes. We show that LD, particularly when administered chronically, caused the development of impulsive-like behaviors in 6-OHDA-lesioned animals in the VDS. However, neither acute or chronic LD administration had rewarding effects in 6-OHDA-lesioned animals in the CPP. Our results show that in a bilateral rat model of PD, LD leads to the development of impulsive behaviors, strengthening the association between DRT and DDS/ICD in PD.

Parkinson's disease (PD) is classically characterized by motor symptoms; however, non-motor symptoms (NMS) are increasingly recognized as relevant in disease-state, given the associated alterations in mood (depression and anxiety) and cognition. Here, particularly in regards to NMS, we aimed to compare the motor, emotional and cognitive behavior of three animal models of PD that trigger dopaminergic (DAergic) degeneration on both brain hemispheres: (i) the 6-hydroxydopamine (6-OHDA, 8 or 6 μg) lesion model; (ii) the paraquat (PQ) induced model, and (iii) a genetic model based on α-synuclein overexpression (α-syn). 6-OHDA and α-syn vector were injected bilaterally in the substantia nigra pars compacta (SNpc) of adult male Wistar rats; as for PQ delivery, micro-osmotic pumps were implanted in the interscapular region. Motor deficits were observed in all models, with histological analysis of tyrosine hydroxylase positive cells in the SNpc revealing a significant loss of DAergic neurons in all animal models. In addition, the α-syn animal model also presented a reduction in exploratory activity, and the 6-OHDA and PQ animals displayed a significant increase in both depressive- and anxiety-like behavior. Interestingly, cognitive impairment (working memory) was only observed in the 6-OHDA model. Overall, these PD models are suitable for mimicking the motor symptoms associated to PD, with each encompassing other relevant NMS components of the disorder that may prove beneficial for further studies in PD.

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

Background: Parkinson's disease (PD) is a chronic neurodegenerative condition that is characterized by motor symptoms as a result of dopaminergic degeneration, particularly in the mesostriatal pathway. However, in recent years, a greater number of clinical studies have focused on the emergence of non-motor symptoms in PD patients, as a consequence of damage on the mesolimbic and mesocortical dopaminergic networks, and on their significant impact on the quality of life of PD patients. Herein, we performed a thorough behavioral analysis including motor, emotional and cognitive dimensions, of the unilateral medial forebrain bundle (MFB) 6-hydroxidopamine (6-OHDA)-lesioned model of PD, and further addressed the impact of pharmacological interventions with levodopa and antidepressants on mood dimensions., Results: Based on apomorphine-induced turning behaviour and degree of dopaminergic degeneration, animals submitted to MFB lesions were subdivided in complete and incomplete lesion groups. Importantly, this division also translated into a different severity of motor and exploratory impairments and depressive-like symptoms; in contrast, no deficits in anxiety-like and cognitive behaviors were found in MFB-lesioned animals. Subsequently, we found that the exploratory and the anhedonic behavioural alterations of MFB-lesioned rats can be partially improved with the administration of both levodopa or the antidepressant bupropion, but not paroxetine., Conclusions: Our results suggest that this model is a relevant tool to study the pathophysiology of motor and non-motor symptoms of PD. In addition, the present data shows that pharmacological interventions modulating dopaminergic transmission are also relevant to revert the non-motor behavioral deficits found in the disease.

The extended amygdala, composed by the amygdaloid nuclei and the bed nucleus of the stria terminalis (BNST), plays a critical role in anxiety behavior. In particular, the link between the central nucleus of the amygdala (CeA) and the BNST seems to be critical to the formation of anxiety-like behavior. Chronic unpredictable stress (CUS) exposure is recognized as a validated animal model of anxiety and is known to trigger significant morphofunctional changes in the extended amygdala. Quite surprisingly, no study has ever analyzed the role of the CeA in the onset of stress-induced anxiety and fear conditioning behaviors; thus, in the present study we induced a bilateral excitotoxic lesion in the CeA of rats that were subsequently exposed to a chronic stress protocol. Data shows that the lesion in the CeA induces different results in anxiety and fear-behaviors. More specifically, lesioned animals display attenuation of the stress response and of stress-induced anxiety-like behavior measured in the elevated-plus maze (EPM) when compared with stressed animals with sham lesions. This attenuation was paralleled by a decrease of stress-induced corticosterone levels. In contrast, we did not observe any significant effect of the lesion in the acoustic startle paradigm. As expected, lesion of the CeA precluded the appearance of fear behavior in a fear-potentiated startle paradigm in both non-stressed and stressed rats. These results confirm the implication of the CeA in fear conditioning behavior and unravel the relevance of this brain region in the regulation of the HPA axis activity and in the onset of anxiety behavior triggered by stress.