Gastroplastia como medida terapêutica em pacientes obesos hipertensos / Gastroplastia as a therapeutic measure in obese hypertensive patients

A hipertensão arterial (HA) e a obesidade são doenças crônicas que se interrelacionam por meio de um quadro complexo de comunicação hormonal e uma série de cascatas enzimáticas. Isso faz com que o manejo dessas comorbidades seja complexo e multifatorial, muitas vezes levando a abandono ou falha terapêutica por parte de pacientes e profissionais de saúde, levando, então, às complicações dessas patologias. Há diversas formas de manejo e a gastroplastia, também conhecida como cirurgia bariátrica, é uma técnica cirúrgica que vem apresentando como alternativa satisfatória para o manejo terapêutico (AU).

Arterial hypertension (AH) and obesity are chronic diseases that are interrelated through a complex framework of hormonal communication and a series of enzymatic cascades. This makes the management of these comorbidities complex and multifactorial, often leading to treatment abandonment or failure by patients and health professionals, thus leading to complications of these pathologies. There are several forms of management and gastroplasty, also known as bariatric surgery, is a surgery that has been presented as a satisfactory alternative for therapeutic management (AU),

Communication of the Diagnosis of Spinal Muscular Atrophy in the Views of Patients and Family Members, a Qualitative Analysis.

INTRODUCTION: Communicating the diagnosis of a genetic and neurodegenerative disease, such as spinal muscular atrophy (SMA), requires a transmission centered on the patient and/or the family caregiver, ensuring autonomy to those involved and strengthening the doctor-patient relationship. OBJECTIVE: Analyzing the communication of the SMA diagnosis from the perspective of patients and family members. METHODS: This qualitative study was developed through semi-structured interviews, via teleconsultation. The analysis was developed by systematically condensing the answers and synthesizing them into four thematic axes (clarification of the diagnosis, communication of the prognosis, affective memory related to the event, and advice to physicians). RESULTS AND DISCUSSION: Twenty-nine patients with SMA and 28 family caregivers of people with this condition, from all regions of Brazil, reported that individualized, clear, honest, and welcoming communication, emphasizing positive aspects, in the presence of family members and with the possibility of continuous monitoring, was important to meeting their communication needs. A lack of empathy, monitoring and guidance, and estimating life expectancy resulted in negative experiences. CONCLUSIONS: The communication needs of patients and family members described during the clarification of the diagnosis and prognosis of SMA predominantly involve empathic factors related to the attitude of the attending physician throughout the evolution of the disease. Future research evaluating other neurodegenerative diseases and the development of research protocols are important to improving communication between physicians, patients, and family members.

Wide spectrum of neuronal and network phenotypes in human stem cell-derived excitatory neurons with Rett syndrome-associated MECP2 mutations.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by heterozygous loss-of-function mutations in the X-linked gene MECP2 that is a global transcriptional regulator. Mutations in the methyl-CpG binding domain (MBD) of MECP2 disrupt its interaction with methylated DNA. Here, we investigate the effect of a novel MECP2 L124W missense mutation in the MBD of an atypical RTT patient with preserved speech in comparison to severe MECP2 null mutations. L124W protein had a limited ability to disrupt heterochromatic chromocenters due to decreased binding dynamics. We isolated two pairs of isogenic WT and L124W induced pluripotent stem cells. L124W induced excitatory neurons expressed stable protein, exhibited increased input resistance and decreased voltage-gated Na+ and K+ currents, and their neuronal dysmorphology was limited to decreased dendritic complexity. Three isogenic pairs of MECP2 null neurons had the expected more extreme morphological and electrophysiological phenotypes. We examined development and maturation of L124W and MECP2 null excitatory neural network activity using micro-electrode arrays. Relative to isogenic controls, L124W neurons had an increase in synchronous network burst frequency, in contrast to MECP2 null neurons that suffered a significant decrease in synchronous network burst frequency and a transient extension of network burst duration. A biologically motivated computational neural network model shows the observed changes in network dynamics are explained by changes in intrinsic Na+ and K+ currents in individual neurons. Our multilevel results demonstrate that RTT excitatory neurons show a wide spectrum of morphological, electrophysiological and circuitry phenotypes that are dependent on the severity of the MECP2 mutation.

Communicating the Spinal Muscular Atrophy diagnosis to children and the principle of autonomy.

INTRODUCTION: The trinomial relationship between physicians/children/guardians is essential in the process of communicating a disease and its prognosis. OBJECTIVE: Analyzing the exercise of autonomy by this trinomial relationship in communicating the diagnosis of spinal muscular atrophy (SMA).   METHODOLOGY: Caregivers of SMA patients answered a questionnaire containing a structured interview and the Event Impact Scale - Revised. RESULTS: The sample comprised 50 volunteers, 94% of whom were female caregivers. Psychological trauma was predominantly reported when caregivers communicated the diagnosis to children. 22% have a high risk of post-traumatic stress, relating the feeling of unpreparedness in communicating this to the child. CONCLUSIONS: It was identified that the failure in communication is the main factor for negative repercussions on the autonomy of children and their guardians, with self-reported psychological trauma, besides the high risk for post-traumatic stress syndrome.

EMPATIA: A Guide for Communicating the Diagnosis of Neuromuscular Diseases.

INTRODUCTION: Neuromuscular diseases comprise a heterogeneous group of genetic syndromes that lead to progressive muscle weakness, resulting in functional limitation. There is a gap in the literature regarding the communication of the diagnosis of such diseases, compromising the autonomy of patients and families, besides causing stress on the assistant physician. OBJECTIVES: Developing a guide to reduce communication barriers in the diagnosis of neuromuscular diseases. METHODOLOGY: Systematic review, after searching the descriptors ("Muscular Diseases" OR "Neuromuscular Diseases") AND ("Truth Disclosure" OR "Bad news communication" OR "Breaking bad News") in the Pubmed, Bireme, and Scopus websites, and these results were analyzed through narrative textual synthesis. RESULTS: 16 articles were submitted to the final analysis, giving rise to seven steps to support the communication process. These are Empathy, Message, Prognosis, Reception, Time, Individualization, and Autonomy. DISCUSSION AND CONCLUSION: The empathic transmission of the message and the prognosis must accommodate the feelings of the interlocutors with different information needs. In this way, communication planning optimizes the time and individualizes each context, respecting the autonomy of those involved. EMPATIA reflects the bioethical and interdisciplinary analysis of the literature and comes to fill the gap related to the communication of bad news in neuromuscular diseases.

A importância do diagnóstico precoce da hipertensão maligna: relato de caso / The importance of early diagnosis of malignant hypertension - case report

A hipertensão maligna é uma síndrome constituída por hipertensão arterial grave, retinopatia com papiledema (com ou sem insuficiência renal) e necrose fibrinóide de arteríolas renais, a qual pode apresentar evolução clínica rapidamente progressiva e fatal.Nela ocorrem lesões vasculares que consistem predominantemente de proliferação miointimal e necrose fibrinóide arteriolar, as quais podem se desenvolver agudamente e comprometer o lúmen dos pequenos vasos. O prognóstico da hipertensão maligna é quase sempre fatal se não for reconhecida ou não for tratada adequadamente, apresentando uma mortalidade de cerca de 80% em dois anos, principalmente em decorrência da evolução para síndrome de insuficiência cardíaca e insuficiência renal terminal.

Malignant hypertension is a syndrome consisting of severe arterial hypertension, retinopathy with papilledema (with or without renal failure) and fibrinoid necrosis of renal arterioles, which may present a rapidly progressive and fatal clinical course. In this pathology may occur vascular lesions that consist mainly of myointimal proliferation and arteriolar fibrinoid necrosis, which can develop acutely and compromise the light from the small blood vessels. The prognosis of malignant hypertension is almost always fatal if it is not recognized or not adequately treated, with a mortality rate of about 80% in 2 years, mainly as a result of progression into heart failure syndrome and end-stage renal failure syndrome.

A importância do diagnóstico precoce da hipertensão maligna: Relato de caso / The importance of early diagnosis of malignant hypertension - Case report

A hipertensão maligna é uma síndrome constituída por hipertensão arterial grave, retinopatia com papiledema (com ou sem insuficiência renal) e necrose fibrinóide de arteríolas renais, a qual pode apresentar evolução clínica rapidamente progressiva e fatal.Nela ocorrem lesões vasculares que consistem predominantemente de proliferação miointimal e necrose fibrinóide arteriolar, as quais podem se desenvolver agudamente e comprometer o lúmen dos pequenos vasos. O prognóstico da hipertensão maligna é quase sempre fatal se não for reconhecida ou não for tratada adequadamente, apresentando uma mortalidade de cerca de 80% em dois anos, principalmente em decorrência da evolução para síndrome de insuficiência cardíaca e insuficiência renal terminal. (AU).

Malignant hypertension is a syndrome consisting of severe arterial hypertension, retinopathy with papilledema (with or without renal failure) and fibrinoid necrosis of renal arterioles, which may present a rapidly progressive and fatal clinical course. In this pathology may occur vascular lesions that consist mainly of myointimal proliferation and arteriolar fibrinoid necrosis, which can develop acutely and compromise the light from the small blood vessels. The prognosis of malignant hypertension is almost always fatal if it is not recognized or not adequately treated, with a mortality rate of about 80% in 2 years, mainly as a result of progression into heart failure syndrome and end-stage renal failure syndrome (AU).

Efficacy of a dinotefuran, pyriproxyfen and permethrin combination product against Ctenocephalides felis felis (Bouché, 1835) (Siphonaptera: Pulicidae) on artificially infested rabbits.

The aim of this study was to evaluate the efficacy of an insecticidal product in rabbits that combines the neonicotinoid dinotefuran with the pyrethroid permethrin plus the insect growth regulator pyriproxyfen. Adult New Zealand rabbits (n = 12) were infested with Ctenocephalides felis felis (50 males and 50 females per rabbit) at days -7, -2, +5, +12 and +19. The control group (n = 6) received no treatment and the treated group (n = 6) received the commercial formulation, indicated for use in dogs, which was applied topically on day 0. The animals were mechanically evaluated with combs (comb test), to assess pulicidal efficacy, on days -5, +2, +7, +14 and +21. All flea removals and counts were performed by region, following the order: head, ears, neck, forelegs, dorsum, abdomen, hind limbs and tail, in order to determine the preferred sites of parasitism by the C. felis felis flea in rabbits. The distribution of fleas prevailed in the head region (about 62%), followed by the neck and back (14 and 11%, respectively). The insecticidal efficacy was calculated using arithmetic means, showing effectiveness of 100% on days +2 and +7 and 82.2% and 81.6%, on days +14 and +21, respectively. Thus the present study has shown the combination to be a viable option in the treatment and control of rabbits infested by C. felis felis.

Author Correction: Blocking Zika virus vertical transmission.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Genetic variations on SETD5 underlying autistic conditions.

The prevalence of autism spectrum disorders (ASD) and the number of identified ASD-related genes have increased in recent years. The SETD5 gene encodes a SET-containing-domain 5 protein, a likely reader enzyme. Genetic evidences suggest that SETD5 malfunction contributes to ASD phenotype, such as on intellectual disability (ID) and facial dysmorphism. In this review, we mapped the clinical phenotypes of individuals carrying mutations on the SETD5 gene that are associated with ASD and other chromatinopathies (mutation in epigenetic modifiers that leads to the development of neurodevelopmental disorders such as ASD). After a detailed systematic literature review and analysis of public disease-related databank, we found so far 42 individuals carrying mutations on the SETD5 gene, with 23.8% presenting autistic-like features. Furthermore, most of mutations occurred between positions 9,480,000-9,500,000 bp on chromosome 3 (3p25.3) at the SETD5 gene locus. In all males, mutations in SETD5 presented high penetrance, while in females the clinical phenotype seems more variable with two reported cases showing normal female carriers and not presenting ASD or any ID-like symptoms. At the molecular level, SETD5 interacts with proteins of PAF1C and N-CoR complexes, leading to a possible involvement with chromatin modification pathway, which plays important roles for brain development. Together, we propose that mutations on the SETD5 gene could lead to a new syndromic condition in males, which is linked to 3p25 syndrome, and can leads to ASD-related intellectual disability and facial dysmorphism. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 500-518, 2018.

Blocking Zika virus vertical transmission.

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity.

Modeling the Interplay Between Neurons and Astrocytes in Autism Using Human Induced Pluripotent Stem Cells.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unclear etiology and imprecise genetic causes. The main goal of this work was to investigate neuronal connectivity and the interplay between neurons and astrocytes from individuals with nonsyndromic ASD using induced pluripotent stem cells. METHODS: Induced pluripotent stem cells were derived from a clinically well-characterized cohort of three individuals with nonsyndromic ASD sharing common behaviors and three control subjects, two clones each. We generated mixed neural cultures analyzing synaptogenesis and neuronal activity using a multielectrode array platform. Furthermore, using an enriched astrocyte population, we investigated their role in neuronal maintenance. RESULTS: ASD-derived neurons had a significant decrease in synaptic gene expression and protein levels, glutamate neurotransmitter release, and, consequently, reduced spontaneous firing rate. Based on co-culture experiments, we observed that ASD-derived astrocytes interfered with proper neuronal development. In contrast, control-derived astrocytes rescued the morphological neuronal phenotype and synaptogenesis defects from ASD neuronal co-cultures. Furthermore, after identifying interleukin-6 secretion from astrocytes in individuals with ASD as a possible culprit for neural defects, we were able to increase synaptogenesis by blocking interleukin-6 levels. CONCLUSIONS: Our findings reveal the contribution of astrocytes to neuronal phenotype and confirm previous studies linking interleukin-6 and autism, suggesting potential novel therapeutic pathways for a subtype of individuals with ASD. This is the first report demonstrating that glial dysfunctions could contribute to nonsyndromic autism pathophysiology using induced pluripotent stem cells modeling disease technology.

Modeling neuro-immune interactions during Zika virus infection.

Although Zika virus (ZIKV) infection is often asymptomatic, in some cases, it can lead to birth defects in newborns or serious neurologic complications in adults. However, little is known about the interplay between immune and neural cells that could contribute to the ZIKV pathology. To understand the mechanisms at play during infection and the antiviral immune response, we focused on neural precursor cells (NPCs)-microglia interactions. Our data indicate that human microglia infected with the current circulating Brazilian ZIKV induces a similar pro-inflammatory response found in ZIKV-infected human tissues. Importantly, using our model, we show that microglia interact with ZIKV-infected NPCs and further spread the virus. Finally, we show that Sofosbuvir, an FDA-approved drug for Hepatitis C, blocked viral infection in NPCs and therefore the transmission of the virus from microglia to NPCs. Thus, our model provides a new tool for studying neuro-immune interactions and a platform to test new therapeutic drugs.

Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis.

One of the major challenges of the current Zika virus (ZIKV) epidemic is to prevent congenital foetal abnormalities, including microcephaly, following ZIKV infection of pregnant women. Given the urgent need for ZIKV prophylaxis and treatment, repurposing of approved drugs appears to be a viable and immediate solution. We demonstrate that the common anti-malaria drug chloroquine (CQ) extends the lifespan of ZIKV-infected interferon signalling-deficient AG129 mice. However, the severity of ZIKV infection in these mice precludes the study of foetal (vertical) viral transmission. Here, we show that interferon signalling-competent SJL mice support chronic ZIKV infection. Infected dams and sires are both able to transmit ZIKV to the offspring, making this an ideal model for in vivo validation of compounds shown to suppress ZIKV in cell culture. Administration of CQ to ZIKV-infected pregnant SJL mice during mid-late gestation significantly attenuated vertical transmission, reducing the ZIKV load in the foetal brain more than 20-fold. Given the limited side effects of CQ, its lack of contraindications in pregnant women, and its worldwide availability and low cost, we suggest that CQ could be considered for the treatment and prophylaxis of ZIKV.

Macroscopic and microscopic analysis of 2 embryos and 1 foetus derived from a sheep (Ovis aries) without breed / Análise macroscópica e microscópica de 2 embriões e 1 feto derivados de ovelha (Ovis aries) sem raça

The interest in embryology, the science of the development of a zygote into a completely developed foetus, has increased greatly in recent years due to a number of studies involving embryonic and induced pluripotent stem cells. In addition, the development of techniques such as cloning has aided to understand the critical events that occur during embryonic development. In this study, we describe the morphology of two sheep embryos and one foetus using macroscopic and microscopic techniques. We investigated sheep without defined breed on days 24, 32, and 50 of gestation (estimated by crown-rump length [CR]). Macroscopically, we observed the development of E1 (24 days), with visible optic vesicle, but without retinal pigmentation and the forelimbs bud in development. In the E2 (32 days), we noticed the presence of optic retinal pigmentation and forelimbs more developed in comparison with E1. As expected, F1 revealed an eyeball already covered and the forelimbs developed. Meanwhile, microscopic analysis revealed somite, ventricle, atrium, and oral cavity in development in E1. However, in F1 we were able to identify more complex structures, such as ossification in the spine, ventricle, atrium, intraventricular septum, pericardial sac, and oral cavity with tongue. This work brings more precise and detailed data on the morphological characteristics of the major organ systems (nervous, circulatory, respiratory, digestive, and urinary) at each embryonic and foetal stage analysed.(AU)

O interesse em Embriologia, a ciência do desenvolvimento de um zigoto em um feto completamente desenvolvido, tem aumentado consideravelmente nos últimos anos devido a uma série de estudos envolvendo células-tronco pluripotentes embrionárias e induzidas. Além disso, o desenvolvimento de técnicas como a clonagem tem ajudado a compreender os eventos críticos que ocorrem durante o desenvolvimento embrionário. Neste estudo, descrevemos a morfologia de dois embriões de ovinos e um feto utilizando técnicas macroscópicas e microscópicas. Obtivemos ovelhas sem raça definida com 24, 32 e 50 dias de gestação (estimado pelo método de Crown-Rump, CR). Os conceptos foram mensurados, pesados e caracterizados a olho nu. Macroscopicamente, observamos o desenvolvimento dos embriões E1 (24 dias), apresentando globo ocular sem pigmentação de retina e broto do membro torácico e pélvico. Já o E2 (32 dias), apresentava globo ocular com pigmentação na retina e os membros torácicos e pélvicos mais desenvolvidos. O F1 apresentou olhos cobertos com uma membrana e membros torácicos e pélvicos mais desenvolvidos. Enquanto isso, microscopicamente observamos no E1 somitos, ventrículo, átrio e cavidade oral ainda em desenvolvimento. Porém, no F1 já era possível observar ossificação da coluna espinhal, coração com estruturas mais complexas, como ventrículo, átrio, septo interventricular e saco pericárdio. Além disso, na cavidade oral observamos a formação da língua. Este trabalho fornece informações precisas e detalhadas sobre as características morfológicas dos principais órgãos dos sistemas (nervoso, circulatório, respiratório, digestivo e urinário) em cada fase embrionária e fetal analisadas.(AU)

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

Dynamic flux chamber measurements of hydrogen sulfide emission rate from a quiescent surface--A computational evaluation.

Enclosure devices have been studied and used for research purposes and practical applications in order to measure the emission rate of odorous pollutants from quiescent liquid surfaces to atmosphere. However, important questions remain about the interference of these measuring devices on the actual emission rate. The main concern regarding the use of a flux chamber is the fact that odorous compounds can accumulate into the chamber and yield gas-phase concentration increase inside the equipment, which causes a reduction of the emission rate during the measurement and thus gives an inaccurate local emission rate. Furthermore, the fluid flow inside the chamber does not reproduce the atmospheric boundary layer flow. This study applied the Computational Fluid Dynamics (CFD) technique in order to investigate the influence of the fluid flow features inside a flux chamber on the measured hydrogen sulfide emission rate at quiescent liquid surfaces. The flux chamber design and operational conditions are those supported by the United States Environmental Protection Agency (US EPA). The results show that the US EPA flux chamber presents a fairly well mixed air phase. However, a trend to stagnation and hydrogen sulfide accumulation near chamber walls was detected in the computational simulation, which also indicated that the positioning of the sampling tube in relation to the inlet orifices may lead to deviations in the measurement results. CFD results showed that the wall shear and concentration gradients spatially vary at the gas-liquid interface, and friction velocity inside the chamber does not match typical values of atmospheric flow.

Potency Evaluation of Recombinant Human Erythropoietin in Brazil: Assessment of Reproducibility Using a Practical Approach

In this study, we compared the results of potency determination of recombinant human erythropoietin (rhEPO) obtained between 2010 and 2012 by the National Institute of Quality Control in Health (INCQS/Fiocruz), i.e., the National Control Laboratory (NCL), and by a manufacturer of rhEPO. In total, 47 different batches of commercially prepared rhEPO (alpha isoform) were analyzed. All results, including those of the control and warning limits, remained within the limits recommended by European Pharmacopoeia (Ph. Eur.). All relative error (RE) values were less than ± 30%, wh ereas most were approximately ± 20%. Applying the Bland-Altman plot, only two of 47 values remained outside the limits of agreement (LA). In addition, agreement of potency determination between INCQS and the manufacturer coefficient of variation of reproducibility (% CVR) was considered satisfactory. Taken together, our results demonstrate (i.) the potency assay of rhEPO performed at INCQS, is standardized and controlled, (ii.) the comparison of our results with those of the manufacturer, revealed an adequate inter-laboratory variation, and (iii.) the critical appraisal proposed here appears to be a feasible tool to assess the reproducibility of biological activity, providing additional information regarding monitoring and production consistency to manufacturers and NCLs.

Aquapuncture Using Stem Cell Therapy to Treat Mdx Mice.

Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to absence or decrease of dystrophin protein generating progressive muscle degeneration. Cell therapy using mesenchymal stem cell (MSC) has been described as a treatment to DMD. In this work, MSC derived from deciduous teeth, called stem cells from human exfoliated deciduous teeth (SHED), were injected in acupoint as an alternative therapy to minimize muscle degeneration in twenty-two mdx mice. The treatment occurred three times with intervals of 21 days, and animals were analyzed four times: seven days prior treatment (T-7); 10 days after first treatment (T10); 10 days after second treatment (T31); and 10 days after third treatment (T52). Animals were evaluated by wire test for estimate strength and blood was collected to perform a creatinine phosphokinase analysis. After euthanasia, cranial tibial muscles were collected and submitted to histological and immunohistochemistry analyses. Treated groups presented improvement of strength and reduced creatinine phosphokinase levels. Also, a slight dystrophin increase was observed in tibial cranial muscle when aquapuncture was associated SHED. All therapies have minimized muscle degeneration, but the association of aquapuncture with SHED appears to have better effect, reducing muscle damage, suggesting a therapeutic value.

Induced pluripotent stem cells for modeling neurological disorders.

Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from iPSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific iPSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using iPSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, Phelan-McDermid, Rett syndrome as well as Nonsyndromic Autism.