A Comprehensive Exploration of Therapeutic Strategies in Inflammatory Bowel Diseases: Insights from Human and Animal Studies.

Inflammatory bowel disease (IBD) is a collective term for a group of chronic inflammatory enteropathies which are characterized by intestinal inflammation and persistent or frequent gastrointestinal signs. This disease affects more than 3.5 million humans worldwide and presents some similarities between animal species, in particular, dogs and cats. Although the underlying mechanism that triggers the disease is not yet well understood, the evidence suggests a multifactorial etiology implicating genetic causes, environmental factors, microbiota imbalance, and mucosa immune defects, both in humans and in dogs and cats. Conventional immunomodulatory drug therapies, such as glucocorticoids or immunosuppressants, are related with numerous adverse effects that limit its long-term use, creating the need to develop new therapeutic strategies. Mesenchymal stromal cells (MSCs) emerge as a promising alternative that attenuates intestinal inflammation by modulating inflammatory cytokines in inflamed tissues, and also due to their pro-angiogenic, anti-apoptotic, anti-fibrotic, regenerative, anti-tumor, and anti-microbial potential. However, this therapeutic approach may have important limitations regarding the lack of studies, namely in veterinary medicine, lack of standardized protocols, and high economic cost. This review summarizes the main differences and similarities between human, canine, and feline IBD, as well as the potential treatment and future prospects of MSCs.

New Multitarget Rivastigmine-Indole Hybrids as Potential Drug Candidates for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia with no cure so far, probably due to the complexity of this multifactorial disease with diverse processes associated with its origin and progress. Several neuropathological hallmarks have been identified that encourage the search for new multitarget drugs. Therefore, following a multitarget approach, nine rivastigmine-indole (RIV-IND) hybrids (5a1-3, 5b1-3, 5c1-3) were designed, synthesized and evaluated for their multiple biological properties and free radical scavenging activity, as potential multitarget anti-AD drugs. The molecular docking studies of these hybrids on the active center of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) suggest their capacity to act as dual enzyme inhibitors with probable greater disease-modifying impact relative to AChE-selective FDA-approved drugs. Compounds 5a3 (IC50 = 10.9 µM) and 5c3 (IC50 = 26.8 µM) revealed higher AChE inhibition than the parent RIV drug. Radical scavenging assays demonstrated that all the hybrids containing a hydroxyl substituent in the IND moiety (5a2-3, 5b2-3, 5c2-3) have good antioxidant activity (EC50 7.8-20.7 µM). The most effective inhibitors of Aß42 self-aggregation are 5a3, 5b3 and 5c3 (47.8-55.5%), and compounds 5b2 and 5c2 can prevent the toxicity induced by Aß1-42 to cells. The in silico evaluation of the drug-likeness of the hybrids also showed that all the compounds seem to have potential oral availability. Overall, within this class of RIV-IND hybrids, 5a3 and 5c3 appear as lead compounds for anti-AD drug candidates, deserving further investigation.

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo.

Background: Abnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. Methods: Fluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively. Results: THK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinson's disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. Conclusion: We demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

Neural and behavioral plasticity across the female reproductive cycle.

Sex is fundamental for the evolution and survival of most species. However, sex can also pose danger, because it increases the risk of predation and disease transmission, among others. Thus, in many species, cyclic fluctuations in the concentration of sex hormones coordinate sexual receptivity and attractiveness with female reproductive capacity, promoting copulation when fertilization is possible and preventing it otherwise. In recent decades, numerous studies have reported a wide variety of sex hormone-dependent plastic rearrangements across the entire brain, including areas relevant for female sexual behavior. By contrast, how sex hormone-induced plasticity alters the computations performed by such circuits, such that collectively they produce the appropriate periodic switches in female behavior, is mostly unknown. In this review, we highlight the myriad sex hormone-induced neuronal changes known so far, the full repertoire of behavioral changes across the reproductive cycle, and the few examples where the relationship between sex hormone-dependent plasticity, neural activity, and behavior has been established. We also discuss current challenges to causally link the actions of sex hormones to the modification of specific cellular pathways and behavior, focusing on rodents as a model system while drawing a comparison between rodents and humans wherever possible.

Natural Age-Related Slow-Wave Sleep Alterations Onset Prematurely in the Tg2576 Mouse Model of Alzheimer's Disease.

INTRODUCTION: Sleep insufficiency or decreased quality have been associated with Alzheimer's disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD. METHODS: We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/electromyography headpieces into 6-month-old (plaque-free, n = 10) and 11-month-old (moderate plaque-burdened, n = 10) Tg2576 mice and age-matched wild-type (WT, 6 months old n = 10, 11 months old n = 10) mice and recorded vigilance states for 24 h. RESULTS: Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-h period compared to WT mice at 6 but not at 11 months of age. Concomitantly, power in the delta frequency was decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, rendering a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 h in the overall sleep-wake phenotype at 11 months of age appears to be the result of changes in sleep-wake characteristics accompanying the healthy aging of WT mice. CONCLUSION: Therefore, our results indicate that at the plaque-free disease stage, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration.

Mesenchymal Stem Cell Studies in the Goat Model for Biomedical Research-A Review of the Scientific Literature.

Mesenchymal stem cells (MSCs) are multipotent cells, defined by their ability to self-renew, while maintaining the capacity to differentiate into different cellular lineages, presumably from their own germinal layer. MSCs therapy is based on its anti-inflammatory, immunomodulatory, and regenerative potential. Firstly, they can differentiate into the target cell type, allowing them to regenerate the damaged area. Secondly, they have a great immunomodulatory capacity through paracrine effects (by secreting several cytokines and growth factors to adjacent cells) and by cell-to-cell contact, leading to vascularization, cellular proliferation in wounded tissues, and reducing inflammation. Currently, MSCs are being widely investigated for numerous tissue engineering and regenerative medicine applications. Appropriate animal models are crucial for the development and evaluation of regenerative medicine-based treatments and eventual treatments for debilitating diseases with the hope of application in upcoming human clinical trials. Here, we summarize the latest research focused on studying the biological and therapeutic potential of MSCs in the goat model, namely in the fields of orthopedics, dermatology, ophthalmology, dentistry, pneumology, cardiology, and urology fields.

Maximum entropy models provide functional connectivity estimates in neural networks.

Tools to estimate brain connectivity offer the potential to enhance our understanding of brain functioning. The behavior of neuronal networks, including functional connectivity and induced connectivity changes by external stimuli, can be studied using models of cultured neurons. Cultured neurons tend to be active in groups, and pairs of neurons are said to be functionally connected when their firing patterns show significant synchronicity. Methods to infer functional connections are often based on pair-wise cross-correlation between activity patterns of (small groups of) neurons. However, these methods are not very sensitive to detect inhibitory connections, and they were not designed for use during stimulation. Maximum Entropy (MaxEnt) models may provide a conceptually different method to infer functional connectivity. They have the potential benefit to estimate functional connectivity during stimulation, and to infer excitatory as well as inhibitory connections. MaxEnt models do not involve pairwise comparison, but aim to capture probability distributions of sets of neurons that are synchronously active in discrete time bins. We used electrophysiological recordings from in vitro neuronal cultures on micro electrode arrays to investigate the ability of MaxEnt models to infer functional connectivity. Connectivity estimates provided by MaxEnt models correlated well with those obtained by conditional firing probabilities (CFP), an established cross-correlation based method. In addition, stimulus-induced connectivity changes were detected by MaxEnt models, and were of the same magnitude as those detected by CFP. Thus, MaxEnt models provide a potentially powerful new tool to study functional connectivity in neuronal networks.

Clinical application of mesenchymal stem cells therapy in musculoskeletal injuries in dogs-a review of the scientific literature.

Mesenchymal stem cells (MSCs) are multipotent, which is defined by their ability to self-renew while maintaining the capacity to differentiate into a certain number of cells, presumably from their own germinal layer. MSCs therapy is based on their anti-inflammatory, immunomodulatory (immunosuppressive), and regenerative potential. This review aims to provide a clinical overview of the MSCs potential as a therapeutic option for orthopedic diseases in dogs. A total of 25 clinical studies published in the scientific literature in the last 15 years on various diseases will be presented: semitendinosus myopathy, supraspinatus tendinopathy, cruciate ligament rupture, bone fractures and defects, and also osteoarthritis (OA). All articles involved in this study include only diseases that have naturally occurred in canine patients. MSCs therapy in the veterinary orthopedic field has great potential, especially for OA. All studies presented promising results. However, MSCs bone healing capacity did not reveal such favorable outcomes in the long term. Besides, most of these clinical studies did not include immunohistochemistry, immunofluorescence, and histopathology to confirm that MSCs have differentiated and incorporated into the injured tissues. This review summarizes the current knowledge of canine MSCs biology, immunology, and clinical application in canine orthopedic diseases. Despite the positive results in its use, there is still a lack of defined protocols, heterogeneous samples, and concomitant medications used with MSCs therapy compromising therapeutic effects. Further studies are needed in the hope of overcoming its limitation in upcoming trials.

Consolidation of memory traces in cultured cortical networks requires low cholinergic tone, synchronized activity and high network excitability.

In systems consolidation, encoded memories are replayed by the hippocampus during slow-wave sleep (SWS), and permanently stored in the neocortex. Declarative memory consolidation is believed to benefit from the oscillatory rhythms and low cholinergic tone observed in this sleep stage, but underlying mechanisms remain unclear. To clarify the role of cholinergic modulation and synchronized activity in memory consolidation, we applied repeated electrical stimulation in mature cultures of dissociated rat cortical neurons with high or low cholinergic tone, mimicking the cue replay observed during systems consolidation under distinct cholinergic concentrations. In the absence of cholinergic input, these cultures display activity patterns hallmarked by network bursts, synchronized events reminiscent of the low frequency oscillations observed during SWS. They display stable activity and connectivity, which mutually interact and achieve an equilibrium. Electrical stimulation reforms the equilibrium to include the stimulus response, a phenomenon interpreted as memory trace formation. Without cholinergic input, activity was burst-dominated. First application of a stimulus induced significant connectivity changes, while subsequent repetition no longer affected connectivity. Presenting a second stimulus at a different electrode had the same effect, whereas returning to the initial stimuli did not induce further connectivity alterations, indicating that the second stimulus did not erase the 'memory trace' of the first. Distinctively, cultures with high cholinergic tone displayed reduced network excitability and dispersed firing, and electrical stimulation did not induce significant connectivity changes. We conclude that low cholinergic tone facilitates memory formation and consolidation, possibly through enhanced network excitability. Network bursts or SWS oscillations may merely reflect high network excitability.

The Structural and Electrophysiological Properties of Progesterone Receptor-Expressing Neurons Vary along the Anterior-Posterior Axis of the Ventromedial Hypothalamus and Undergo Local Changes across the Reproductive Cycle.

Sex hormone levels continuously fluctuate across the reproductive cycle, changing the activity of neuronal circuits to coordinate female behavior and reproductive capacity. The ventrolateral division of the ventromedial hypothalamus (VMHvl) contains neurons expressing receptors for sex hormones and its function is intimately linked to female sexual receptivity. However, recent findings suggest that the VMHvl is functionally heterogeneous. Here, we used whole recordings and intracellular labeling to characterize the electrophysiological and morphologic properties of individual VMHvl neurons in naturally cycling females and report the existence of multiple electrophysiological phenotypes within the VMHvl. We found that the properties of progesterone receptor expressing (PR+) neurons, but not PR- neurons, depended systematically on the neuron's location along the anterior-posterior (AP) axis of the VMHvl and the phase within the reproductive cycle. Prominent among this, the resting membrane potential of anterior PR+ neurons decreased during the receptive phase, while the excitability of medial PR+ neurons increased during the non-receptive phase. During the receptive phase of the cycle, posterior PR+ neurons simultaneously showed an increase in dendritic complexity and a decrease in spine density. These findings reveal an extensive diversity of local rules driving structural and physiological changes in response to fluctuating levels of sex hormones, supporting the anatomic and functional subdivision of the VMHvl and its possible role in the orchestration of different aspects of female socio-sexual behavior.

Salmonella spp. in Pet Reptiles in Portugal: Prevalence and Chlorhexidine Gluconate Antimicrobial Efficacy.

A fraction of human Salmonella infections is associated with direct contact with reptiles, yet the number of reptile-associated Salmonellosis cases are believed to be underestimated. Existing data on Salmonella spp. transmission by reptiles in Portugal is extremely scarce. The aim of the present work was to evaluate the prevalence of Salmonella spp. in pet reptiles (snakes, turtles, and lizards), as well as evaluate the isolates' antimicrobial resistance and virulence profiles, including their ability to form biofilm in the air-liquid interface. Additionally, the antimicrobial effect of chlorhexidine gluconate on the isolates was tested. Salmonella was isolated in 41% of the animals sampled and isolates revealed low levels of antimicrobial resistance. Hemolytic and lypolytic phenotypes were detected in all isolates. The majority (90.63%) of the Salmonella isolates were positive for the formation of pellicle in the air-liquid interface. Results indicate chlorhexidine gluconate is an effective antimicrobial agent, against the isolates in both their planktonic and biofilm forms, demonstrating a bactericidal effect in 84.37% of the Salmonella isolates. This study highlights the possible role of pet reptiles in the transmission of non-typhoidal Salmonella to humans, a serious and increasingly relevant route of exposure in the Salmonella public health framework.

Chronic hyperglycemia impairs hippocampal neurogenesis and memory in an Alzheimer's disease mouse model.

During aging, lifestyle-related factors shape the brain's response to insults and modulate the progression of neurodegenerative pathologies such as Alzheimer's disease (AD). This is the case for chronic hyperglycemia associated with type 2 diabetes, which reduces the brain's ability to handle the neurodegenerative burden associated with AD. However, the mechanisms behind the effects of chronic hyperglycemia in the context of AD are not fully understood. Here, we show that newly generated neurons in the hippocampal dentate gyrus of triple transgenic AD (3xTg-AD) mice present increased dendritic arborization and a number of synaptic puncta, which may constitute a compensatory mechanism allowing the animals to cope with a lower neurogenesis rate. Contrariwise, chronic hyperglycemia decreases the complexity and differentiation of 3xTg-AD newborn neurons and reduces the levels of ß-catenin, a key intrinsic modulator of neuronal maturation. Moreover, synaptic facilitation is depressed in hyperglycemic 3xTg-AD mice, accompanying the defective hippocampal-dependent memory. Our data suggest that hyperglycemia evokes cellular and functional alterations that accelerate the onset of AD-related symptoms, namely memory impairment.

A Prime-Boost Immunization Strategy with Vaccinia Virus Expressing Novel gp120 Envelope Glycoprotein from a CRF02_AG Isolate Elicits Cross-Clade Tier 2 HIV-1 Neutralizing Antibodies.

Development of new immunogens eliciting broadly neutralizing antibodies (bNAbs) is a main priority for the HIV-1 vaccine field. Envelope glycoproteins from non-B-non-C HIV-1clades have not been fully explored as components of a vaccine. We produced Vaccinia viruses expressing a truncated version of gp120 (gp120t) from HIV-1 clades CRF02_AG, H, J, B, and C and examined their immunogenicity in mice and rabbits. Mice primed with the recombinant Vaccinia viruses and boosted with the homologous gp120t or C2V3C3 polypeptides developed antibodies that bind potently to homologous and heterologous envelope glycoproteins. Notably, a subset of mice immunized with the CRF02_AG-based envelope immunogens developed a cross-reactive neutralizing response against tier 2 HIV-1 Env-pseudoviruses and primary isolates. Rabbits vaccinated with the CRF02_AG-based envelope immunogens also generated potent binding antibodies, and one animal elicited antibodies that neutralized almost all (13 of 16, 81.3%) tier 2 HIV-1 isolates tested. Overall, the results suggest that the novel CRF02_AG-based envelope immunogens and prime-boost immunization strategy elicit the type of immune responses required for a preventive HIV-1 vaccine.

[A New Paradigm in Health Research: FAIR Data (Findable, Accessible, Interoperable, Reusable)]. / Um Novo Paradigma em Investigação em Saúde: Dados FAIR (Localizáveis, Acessíveis, Interoperáveis, Reutilizáveis).

The digital era, that we are living nowadays, is transforming health, health care models and services, and the role of society in this new reality. We currently have a large amount of stored health data, including clinical, biometric, and scientific research data. Nonetheless, its potential is not being fully exploited. It is essential to foster the sharing and reuse of this data not only in research but also towards the development of health technologies in order to improve health care efficiency, as well as products, services or digital health apps, to promote preventive and individualized medicine and to empower citizens in health literacy and self-management. In this sense, the FAIR concept has emerged, which implies that health data is findable, accessible, shared and reusable, facilitating interoperability between systems, ensuring the protection of personal and sensitive data. In this paper we review the FAIR concept, 'FAIRification' process, FAIR data versus open access data, ethical issues and the general data protection regulation, and digital health and citizen science.

Vivemos uma nova era digital que está a transformar a saúde, os modelos de cuidados e serviços de saúde, e o próprio papel da sociedade nesta realidade. Atualmente dispomos de uma grande quantidade de dados de saúde armazenados, incluindo dados clínicos, biométricos e de investigação científica, cuja potencialidade não está a ser devidamente explorada. É essencial favorecer a partilha e reutilização destes dados não só na investigação, como também para o desenvolvimento de tecnologias para melhorar a eficiência dos cuidados de saúde, de produtos ou serviços de saúde digitais, promover uma medicina preventiva e individualizada, mas também o empoderamento da população em literacia em saúde e na gestão da doença. Recentemente, surgiu o conceito FAIR que implica que os dados de saúde sejam facilmente localizáveis, acessíveis, partilhados e reutilizáveis, facilitando desta forma a interoperacionalidade entre sistemas e assegurando a proteção de dados pessoais e sensíveis. Neste artigo é feita uma revisão do conceito FAIR, processo de 'FAIRificação', dados FAIR versus dados de acesso livre, questões de éticas e o regulamento geral de proteção de dados, e saúde digital e ciência cidadã.

Mesenchymal stem cells therapy in companion animals: useful for immune-mediated diseases?

Mesenchymal stem cells are multipotent cells, with capacity for self-renewal and differentiation into tissues of mesodermal origin. These cells are possible therapeutic agents for autoimmune disorders, since they present remarkable immunomodulatory ability.The increase of immune-mediated diseases in veterinary medicine has led to a growing interest in the research of these disorders and their medical treatment. Conventional immunomodulatory drug therapy such as glucocorticoids or other novel therapies such as cyclosporine or monoclonal antibodies are associated with numerous side effects that limit its long-term use, leading to the need for developing new therapeutic strategies that can be more effective and safe.The aim of this review is to provide a critical overview about the therapeutic potential of these cells in the treatment of some autoimmune disorders (canine atopic dermatitis, feline chronic gingivostomatitis, inflammatory bowel disease and feline asthma) compared with their conventional treatment.Mesenchymal stem cell-based therapy in autoimmune diseases has been showing that this approach can ameliorate clinical signs or even cause remission in most animals, with the exception of canine atopic dermatitis in which little to no improvement was observed.Although mesenchymal stem cells present a promising future in the treatment of most of these disorders, the variability in the outcomes of some clinical trials has led to the current controversy among authors regarding their efficacy. Mesenchymal stem cell-based therapy is currently requiring a deeper and detailed analysis that allows its standardization and better adaptation to the intended therapeutic results, in order to overcome current limitations in future trials.

Prevalence and risk factors for food allergy in older people: protocol for a systematic review.

INTRODUCTION: Studies suggest that the prevalence of food allergy may be increasing worldwide. Results regarding the prevalence and features of adverse food reactions older people have, however, scarcely been analysed in the literature. Thus, the objective of the present systematic review will be to describe the prevalence of food allergy in older individuals, its risk factors, clinical features, as well as the most frequently and commonly involved foods. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of the incidence, prevalence and risk factors for food allergy in older individuals. We will search international electronic databases including MEDLINE, EMBASE, Cochrane Library, CINAHL, AMED and ISI Web of Science for published, unpublished and ongoing studies from 1980 toJanuary 2019. There will be no restriction on the language or geography of publication. We will use the critical appraisal skills programme quality assessment tool to appraise the methodological quality of included studies. A descriptive summary with data tables will be elaborated, and if deemed clinically relevant and statistically adequate, meta-analysis using random-effects modelling will be carried out, given the expected clinical, methodological and statistical heterogeneity of studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will guide reporting of the systematic review. ETHICS AND DISSEMINATION: Since this systematic review will be solely based on published and retrievable literature, no ethics approval will be obtained. This study will allow us to draw up-to-date estimates of the prevalence of adverse food reactions in older individuals, worldwide, besides allowing the identification of its major risk factors, clinical manifestations and predominant foods responsible for such reactions. A multidisciplinary team has been assembled for this systematic review and will participate in relevant dissemination activities, namely reports, publications and presentations. PROSPERO REGISTRATION NUMBER: CRD42018102140.

What are the most frequent diagnoses in adolescence? The reality of an Adolescent Medicine Clinic.

OBJECTIVE: To characterize the care flow and the primary diagnoses of an Adolescent Medicine Clinic. METHODS: A retrospective descriptive study, with analysis of clinical processes of adolescents (10-18 years) seen at the Adolescent Medicine Clinic, from January 2006 to December 2013. The following variables were analyzed: sex, age, number of visits, referring service and primary diagnoses according to the International Statistical Classification of Diseases and Related Health Problems. As to the variable age, the adolescents were divided into two groups: Group I comprised those aged 10-14 years, and Group II, 15-18 years. RESULTS: A total of 7,692 visits were carried out, in that, 1,659 first visits (22%), with an annual growth rate of 6%. The mean age was 14.2 years, and 55% of patients were female. The group of endocrine, nutritional and metabolic diseases was the most representative in our sample (34%), with obesity being the most frequent diagnosis in both sexes and age groups (23%), with a higher prevalence in males (13% male versus 10% female, p<0.001) and younger adolescents (18% in Group I versus 5% in Group II p<0.001). The group of mental and behavioral disorders was the second most prevalent (32%), affecting mainly females (39% female versus 22% male, p<0.001) and the older age group (39% Group II versus 27% Group I, p<0.001). Social problems were the primary diagnosis in 8% of visits. CONCLUSION: Most diseases diagnosed have a strong behavioral and social component, particularly mental disorders and obesity. This specific type of diagnoses reinforces the need for a global approach for adolescents and specialized adolescent medicine units/clinics.

What are the most frequent diagnoses in adolescence? The reality of an Adolescent Medicine Clinic / Quais os diagnósticos mais frequentes na adolescência? A realidade de uma consulta de Medicina do Adolescente

ABSTRACT Objective To characterize the care flow and the primary diagnoses of an Adolescent Medicine Clinic. Methods A retrospective descriptive study, with analysis of clinical processes of adolescents (10-18 years) seen at the Adolescent Medicine Clinic, from January 2006 to December 2013. The following variables were analyzed: sex, age, number of visits, referring service and primary diagnoses according to the International Statistical Classification of Diseases and Related Health Problems. As to the variable age, the adolescents were divided into two groups: Group I comprised those aged 10-14 years, and Group II, 15-18 years. Results A total of 7,692 visits were carried out, in that, 1,659 first visits (22%), with an annual growth rate of 6%. The mean age was 14.2 years, and 55% of patients were female. The group of endocrine, nutritional and metabolic diseases was the most representative in our sample (34%), with obesity being the most frequent diagnosis in both sexes and age groups (23%), with a higher prevalence in males (13% male versus 10% female, p<0.001) and younger adolescents (18% in Group I versus 5% in Group II p<0.001). The group of mental and behavioral disorders was the second most prevalent (32%), affecting mainly females (39% female versus 22% male, p<0.001) and the older age group (39% Group II versus 27% Group I, p<0.001). Social problems were the primary diagnosis in 8% of visits. Conclusion Most diseases diagnosed have a strong behavioral and social component, particularly mental disorders and obesity. This specific type of diagnoses reinforces the need for a global approach for adolescents and specialized adolescent medicine units/clinics.

RESUMO Objetivo Caracterizar o movimento assistencial e conhecer os diagnósticos principais de uma consulta de Medicina do Adolescente. Métodos Estudo descritivo retrospectivo, com análise dos processos clínicos dos adolescentes (10 a 18 anos) seguidos na consulta de Medicina do Adolescente, de janeiro de 2006 a dezembro de 2013. Foram analisadas as variáveis: sexo, idade, número de consultas, entidade que referenciou e diagnósticos principais, de acordo com a Classificação Estatística Internacional de Doenças e Problemas Relacionados com a Saúde. Com relação à variável idade, os adolescentes foram divididos em dois grupos: Grupo I, que incluiu adolescentes de 10 a 14 anos, e Grupo II, que incluiu aqueles com 15 aos 18 anos. Resultados Realizaram-se 7.692 consultas, sendo 1.659 (22%) primeiras consultas, com taxa de crescimento anual de 6%. A média de idade foi de 14,2 anos, com 55% do sexo feminino. O grupo das doenças endócrinas, nutricionais e metabólicas foi o mais representativo da amostra (34%), sendo a obesidade o diagnóstico mais frequente em ambos os sexos e grupos etários (23%), com maior prevalência nos rapazes (13% homens versus 10% mulheres; p<0,001) e nos adolescentes mais jovens (18% do Grupo I versus 5% do Grupo II; p<0,001). O grupo dos transtornos mentais e do comportamento foi o segundo mais prevalente (32%), afetando principalmente as adolescentes (39% mulheres versus 22% homens; p<0,001) e o grupo etário mais velho (39% do Grupo II versus 27% do Grupo I; p<0,001). Problemas sociais constituíram o principal diagnóstico em 8% das consultas. Conclusão A maioria das patologias diagnosticadas tem forte componente comportamental e social, com destaque para as doenças mentais e a obesidade. Esta tipologia específica de diagnósticos evidencia a necessidade de uma abordagem global do adolescente e de unidades/consultas especializadas nesta faixa etária.

Design of Finasteride-Loaded Nanoparticles for Potential Treatment of Alopecia.

BACKGROUND/AIMS: Androgenetic alopecia is an extremely common dermatological disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza-3-oxosteroid compound with poor aqueous solubility, blocks the peripheral conversion of testosterone to dihydrotestosterone (DHT) in a significant reduction in DHT concentration, achieving satisfactory results in alopecia treatment. However, its oral intake generally causes severe side effects. Considering that there is currently no scientifically proven treatment, new drug delivery systems able to improve alopecia therapy are urgently required. METHODS: In this study, polymeric nanoparticles have been proposed as a new carrier for topical delivery of FNS in hair follicles. RESULTS AND CONCLUSIONS: Polymeric nanoparticles, prepared by using a modified method of the emulsification/solvent diffusion, showed a mean particle size around 300 nm, which may be sufficient for reaching the dermis and hair follicles and negative zeta potential values. Scanning electron microscope measurements showed that all the polymeric nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. A high encapsulation efficiency was achieved for FNS (79.49 ± 0.47%). In vitro release assays in physiological conditions demonstrated that nanoparticles yielded a prolonged release of FNS for 3 h. Skin assays through an in vitro permeation study demonstrated that nanoparticles had low levels of penetration of FNS, improving its time residence onto the skin. All excipients used in nanoparticle composition and in 3 different vehicles were safe. These results suggest that the proposed novel formulation presents several good characteristics indicating its suitability for dermal delivery of FNS for alopecia treatment.