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Este estudo aborda o quanto é importante realizar a análise tributária para definir qual o meio de tributação mais adequado durante a constituição da empresa, com o intuito de reduzir elevadas cargas tributarias. A metodologia utilizada foi mediante a levantamento bibliográfico, elaboração de planilhas de cálculos, conjunto de informações de uma empresa com dados fictícios para a demonstração de como cada regime atua, onde o método utilizado foi o qualitativo. Ainda foram realizadas comparações entre os regimes tributários com ênfase em tributos federais (Imposto de Renda Pessoa Jurídica e na Contribuição Social sobre o Lucro), a fim de demonstrar qual forma de tributação seria a mais vantajosa. Tais análises demonstraram que o regime tributário mais benéfico e com cargas tributárias mais reduzidas seria o Lucro Presumido.

O presente Trabalho de Conclusão de Curso tem como finalidade expor os procedimentos necessários para a regular transformação do Microempreendedor Individual para a Microempresa. Utilizou-se da metodologia de análise descritiva de bibliografias já existentes sobre o tema. Como resultado, nota-se que a formalização da transição se faz mediante procedimentos principalmente administrativos e contábeis, quais sejam a comunicação do desenquadramento no portal do Simples Nacional, o preenchimento do Formulário de Desenquadramento e o Requerimento do Empresário. Com a regularização desses documentos, faz-se o depósito na Junta Comercial do estado e tem-se a formalização da migração. Contudo, essa mudança culmina na aquisição de maiores obrigações tributárias, fiscais e administrativas e a não comunicação do ente governamental competente importa na aplicação de infrações e penalidades, como multas.

O Simples Nacional é um dos regimes tributários oferecidos pelo sistema tributário nacional. Especialmente voltado as microempresas e empresas de pequeno porte, sua função é simplificar a forma de arrecadação através da unificação no pagamento e sintetização das obrigações iniciais e acessórias. Regida pela Lei Complementar nº 123 de 14 de dezembro de 2006, o Simples apresenta 5 anexos, cada contendo uma tabela com as alíquotas para os respectivos ramos. O objetivo deste artigo é apresentar a aplicação dos anexos, utilizando de uma atividade empresarial aleatória de cada anexo para o cálculo. Os resultados dessa pesquisa expõem a prática dessa simplificação e os benefícios que ela traz aos inseridos no regime.

With an aging population, the presence of aging-associated pathologies is expected to increase within the next decades. Regrettably, we still do not have any valid pharmacological or non-pharmacological tools to prevent, revert, or cure these pathologies. The absence of therapeutical approaches against aging-associated pathologies can be at least partially explained by the relatively lack of knowledge that we still have regarding the molecular mechanisms underlying them, as well as by the complexity of their etiopathology. In fact, a complex number of changes in the physiological function of the cell has been described in all these aging-associated pathologies, including neurodegenerative disorders. Based on multiple scientific manuscripts produced by us and others, it seems clear that mitochondria are dysfunctional in many of these aging-associated pathologies. For example, mitochondrial dysfunction is an early event in the etiopathology of all the main neurodegenerative disorders, and it could be a trigger of many of the other deleterious changes which are present at the cellular level in these pathologies. While mitochondria are complex organelles and their regulation is still not yet entirely understood, inorganic polyphosphate (polyP) could play a crucial role in the regulation of some mitochondrial processes, which are dysfunctional in neurodegeneration. PolyP is a well-preserved biopolymer; it has been identified in every organism that has been studied. It is constituted by a series of orthophosphates connected by highly energetic phosphoanhydride bonds, comparable to those found in ATP. The literature suggests that the role of polyP in maintaining mitochondrial physiology might be related, at least partially, to its effects as a key regulator of cellular bioenergetics. However, further research needs to be conducted to fully elucidate the molecular mechanisms underlying the effects of polyP in the regulation of mitochondrial physiology in aging-associated pathologies, including neurodegenerative disorders. With a significant lack of therapeutic options for the prevention and/or treatment of neurodegeneration, the search for new pharmacological tools against these conditions has been continuous in past decades, even though very few therapeutic approaches have shown potential in treating these pathologies. Therefore, increasing our knowledge about the molecular mechanisms underlying the effects of polyP in mitochondrial physiology as well as its metabolism could place this polymer as a promising and innovative pharmacological target not only in neurodegeneration, but also in a wide range of aging-associated pathologies and conditions where mitochondrial dysfunction has been described as a crucial component of its etiopathology, such as diabetes, musculoskeletal disorders, and cardiovascular disorders.

Background This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing odontogenic cysts. Material and Methods A systematic review was conducted according to the PRISMA statements and considering eleven databases, including the grey literature. Protocol was registered in PROSPERO (CRD 42020189349). The PECO strategy was used to define the eligibility criteria and only studies involving diagnostic accuracy were included. Their risk of bias was investigated using the Joanna Briggs Institute Critical Appraisal tool. Results Out of 437 identified citations, five papers, published between 2006 and 2019, fulfilled the criteria and were included in this systematic review. A total of 5,264 images from 508 lesions, classified as radicular cyst, odontogenic keratocyst, lateral periodontal cyst, glandular odontogenic cyst, or dentigerous cyst, were analyzed. All selected articles scored low risk of bias. In three studies, the best performances were achieved when the two subtypes of odontogenic keratocysts (solitary or syndromic) were pooled together, the case-wise analysis showing a success rate of 100% for odontogenic keratocysts and radicular cysts, in one of them. In two studies, the dentigerous cyst was associated with the majority of misclassifications, and its omission from the dataset improved significantly the classification rates. Conclusions The overall evaluation showed all studies presented high accuracy rates of computer-aided systems in classifying odontogenic cysts in digital images of histological tissue sections. However, due to the heterogeneity of the studies, a meta-analysis evaluating the outcomes of interest was not performed and a pragmatic recommendation about their use is not possible. Key words:Computer-assisted diagnosis, computer-assisted image analysis, computer-assisted image processing, odontogenic cysts, keratocysts, radicular cysts.

Objectives The low resistance to fracture has limited the use of indirect composite resins for dental restorations, particularly in regions that are exposed to strong occlusal forces. To overcome this issue, different types of reinforcement for composites have been proposed, one of which is carbon nanotubes (CNTs). The aim of this study was to evaluate the flexural resistance of one commercial indirect composite resin (Sinfony, 3M/ESPE) after incorporation of single-wall carbon nanotubes (SWCNTs; Sigma–Aldrich, Inc., St. Louis, Missouri, United States) with or without the silanization form. Materials and Methods Specimens of composite resin were fabricated in a Teflon mold. The composite resin was prepared according to the manufacturer’s instructions (n = 10 for each group), with SWCNTs in three concentrations. Statistical Analysis The SWCNTs and SWCNT/SiO2-ATES specimens were evaluated by transmission electron microscopy, and a flexural test was conducted according to the ISO 4049/2009. Flexural strength data in MPa were submitted to one-way ANOVA following Tukey (p < 0.05). Results The SWCNTs did not improve the flexural strength of indirect composite resin when compared with the control, independent of the concentration added (p > 0.05). However, when SWCNTs and SWCNTs/SiO2-ATES were compared, the SWCNTs/SiO2-ATES showed higher values than the three concentrations of SWCNTs (p < 0.05). Conclusion The silanization process improves the SWCNTs strength proprieties, but the modification of chemical bonding between SWCNT and SWCNT/SiO2-ATES modified resins, in different concentrations, did not improve the composite resin flexural strength.

Congenital erythropoietic porphyria (CEP), also known as Günther’s disease, results from a deficient activity in the fourth enzyme, uroporphyrinogen III synthase (UROIIIS), of the heme pathway. Ciclopirox (CPX) is an off-label drug, topically prescribed as an antifungal. It has been recently shown that it also acts as a pharmacological chaperone in CEP, presenting a specific activity in deleterious mutations in UROIIIS. Despite CPX is active at subtoxic concentrations, acute gastrointestinal (GI) toxicity was found due to the precipitation in the stomach of the active compound and subsequent accumulation in the intestine. To increase its systemic availability, we carried out pharmacokinetic (PK) and pharmacodynamic (PD) studies using alternative formulations for CPX. Such strategy effectively suppressed GI toxicity in WT mice and in a mouse model of the CEP disease (UROIIISP248Q/P248Q). In terms of activity, phosphorylation of CPX yielded good results in CEP cellular models but showed limited activity when administered to the CEP mouse model. These results highlight the need of a proper formulation for pharmacological chaperones used in the treatment of rare diseases.

Chloroquine and hydroxychloroquine are 2 medications used to treat some systemic diseases.The aim of this scoping review was to assess the occurrence of oral pigmentation induced by chloroquine or hydroxychloroquine and to understand the pathogenic mechanism behind this phenomenon.The review was performed according to the list of PRISMA SrC recommendations and the JBI Manual for Evidence Synthesis for Scoping Reviews. MEDLINE (PubMed), Scopus, EMBASE, SciELO, Web of Science, Lilacs, and LIVIVO were primary sources, and "gray literature" was searched in OpenThesis and Open Access Thesis and Dissertations (OATD). Studies that screened the occurrence of oral pigmentation associated to the use of chloroquine or hydroxychloroquine were considered eligible. No restrictions of year and language of publication were applied. Study selection and data extraction were performed by 2 independent reviewers. The risk of bias was assessed through the JBI tool, depending on the design of the selected studies.The initial search resulted in 2238 studies, of which 19 were eligible. Sixteen studies were case reports, 2 had case-control design and 1 was cross-sectional. Throughout the studies, 44 cases of oral pigmentation were reported. The hard palate was the anatomic region most affected with pigmentation (66%). According to the case reports, most of the lesions (44%) were bluish-gray. The minimum time from the beginning of treatment (chloroquine or hydroxychloroquine) to the occurrence of pigmentation was 6 months. The mean treatment time with the medications was 4.9 years, and the mean drug dosage was 244 mg. Most of the studies (63.1%) had low risk of bias (high methodological quality).The outcomes of this study suggest that hyperpigmentation depend on drug dosage and treatment length. Hyperpigmentation was detected after a long period of treatment with chloroquine or hydroxychloroquine.

COVID‐19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 is not only a lung disease but rather a systemic syndrome where blood alterations may play a key role (1). Severe cases show a marked variation in the red blood cell distribution width (2), which agrees well with reduced erythrocyte turnover and would function as a compensatory mechanism to maintain the circulating red blood cell and oxygen levels (3).

Mitochondrial dysfunction – including increased apoptosis, calcium and protein dyshomeostasis within the organelle, and dysfunctional bioenergetics and oxidative status – is a common, early feature in all the major neurodegenerative diseases, including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). However, the exact molecular mechanisms that drive the organelle to dysfunction and ultimately to failure in these conditions are still not well described. Different authors have shown that inorganic polyphosphate (polyP), an ancient and well-conserved molecule, plays a key role in the regulation of mitochondrial physiology under basal conditions. PolyP, which is present in all studied organisms, is composed of chains of orthophosphates linked together by highly energetic phosphoanhydride bonds, similar to those found in ATP. This polymer shows a ubiquitous distribution, even if a high co-localization with mitochondria has been reported. It has been proposed that polyP might be an alternative to ATP for cellular energy storage in different organisms, as well as the implication of polyP in the regulation of many of the mitochondrial processes affected in AD and PD, including protein and calcium homeostasis. Here, we conduct a comprehensive review and discussion of the bibliography available regarding the role of polyP in the mitochondrial dysfunction present in AD and PD. Taking into account the data presented in this review, we postulate that polyP could be a valid, innovative and, plausible pharmacological target against mitochondrial dysfunction in AD and PD. However, further research should be conducted to better understand the exact role of polyP in neurodegeneration, as well as the metabolism of the polymer, and the effect of different lengths of polyP on cellular and mitochondrial physiology.

Background Primary burning mouth syndrome (BMS) is a chronic clinical condition of idiopathic mainly characterized by pain and a burning sensation in the oral cavity. The application of laser at low intensity therapy is a treatment option. This systematic review evaluated the efficacy of laser therapy in treating symptoms of burning mouth syndrome. Material and Methods The study was formulated according to the PRISMA and Cochrane guidelines. Seven databases were used as primary sources of research. Only randomized controlled clinical trials were included. The efficacy of the therapy was estimated comparing the values of the visual and numerical scales of pain before and after laser treatment, through qualitative analysis. Results The search resulted in 348 records and only eight filled the eligibility criteria and were included. All studies evaluated pain and / or a burning sensation considering a time interval of two to ten weeks. The total sample consisted of 314 patients submitted to treatment: 123 from the control group, who participated with laser off or with the tip blocked, and 191 from the intervention group, treated with low-level laser therapy. The female gender stood out and the average age of the participants was 60.89 years. The main symptoms reported were pain and a burning sensation in the oral mucosa and tongue. The parameters adopted by the authors for laser treatment were diverse and the variables were not fully described in the published studies. Visual analog and numerical scales were used to assess symptoms and only three studies showed statistical significance. Conclusions It is suggested that laser therapy may be an effective alternative in the treatment of BMS. New randomized clinical trials should consider well-established protocols to better understand the efficacy of laser therapy without confounding the effects. Key words:Efficacy, systematic review, burning mouth syndrome, low level laser therapy.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior A pneumonia associada à ventilação (PAV) é uma infecção pulmonar que se desenvolve em um paciente colocado em ventilação mecânica por mais de 48 horas. É a infecção no trato respiratório inferior mais comum em pacientes sob ventilação mecânica. A higiene oral é um importante fator na prevenção da PAV. A clorexidina é um antisséptico de efeito bacteriostático e bactericida, e seu efeito pode ser potencializadopela remoção mecânica de microrganismos através da escovação dental. O objetivo deste trabalho foi comparar a eficácia da clorexidina 0,12% versus clorexidina 0,12% associada à escovação mecânica na prevenção da PAV. Para tando, foi realizada inicialmente uma revisão sistemática de ensaios clínicos randomizados seguindo as diretrizes PRISMA-P e Cochrane. Em seguida, uma metanálise foi realizada com publicações que houvessem informado a frequência de PAV nos grupos de interesse deste estudo. Foram identificados inicialmente 2.337 trabalhos, dos quais quatro foram considerados na revisão sistemática e três na metanálise. Os estudos incluídos apresentaram baixo risco de viés. Todos os trabalhos considerados na revisão sistemática mostraram frequência menor de PAV em pacientes submetidos a protocolo de higiene oral com escovação associada à clorexidina, comparados ao uso exclusivo de clorexidina, todavia em nenhum deles essa diferença foi estatisticamente significativa. Na metanálise, os resultados agregados revelaram que o risco de PAV era 24% menor para pacientes que receberam CHX e escovação de dentes em comparação com aqueles que receberam CHX apenas, mas essa redução tampouco se mostrou estatisticamente significativa. Conclusão: Houve convergência dos resultados dos estudos quanto a efeito benéfico do uso combinado da escovação e clorexidina, todavia os resultados agregados desses estudos não resultaram em diferença significativa na frequência de PAV. Ventilator-associated pneumonia (VAP) is a pulmonary infection that develops in a patient on mechanical ventilation for more than 48 hours. It is the most common lower respiratory tract infection in mechanically ventilated patients. Oral hygiene is an important factor in preventing VAP. Chlorhexidine is an antiseptic with bacteriostatic and bactericidal effect, and its effect can be potentiated by mechanical removal of microorganisms through tooth brushing. The aim of this study was to compare the efficacy of 0.12% chlorhexidine versus 0.12% chlorhexidine associated with mechanical brushing to prevent VAP. However, a systematic review of randomized controlled trials was initially performed following the PRISMA-P and Cochrane guidelines. Then, a meta-analysis was performed with publications that reported the frequency of VAP in the interest groups of this study. Initially, 2,337 studies were identified, four of which were considered in the systematic review and three in the meta-analysis. The included studies had a low risk of bias. All studies considered in the systematic review showed a lower frequency of VAP in patients undergoing chlorhexidine-associated oral hygiene protocol compared to the exclusive use of chlorhexidine, but in none of them this difference was statistically significant. In the meta-analysis, aggregated results revealed that the risk of VAP was 24% lower for patients receiving CHX and tooth brushing compared with those receiving CHX alone, but this reduction was not statistically significant either. Conclusion: There was convergence of study results regarding the beneficial effect of combined use of brushing and chlorhexidine, however the aggregated results of these studies did not result in significant difference in VAP frequency. Dissertação (Mestrado) 2022-02-13

Erythema multiforme is an uncommon acute inflammatory disorder caused by exposure to microbes or drugs. Erythema multiforme minor typically affects only one mucosa and can be associated with symmetrical target skin lesions on the extremities. The disease usually occurs in patients in their 3rd and 4th decade of life, but can also affect children and adolescents. Alendronate sodium has been approved for the prevention and treatment of osteoporosis in postmenopausal women, but is associated with adverse events. This study reports and discusses a case of erythema multiforme minor. In addition, a literature search of articles published in PubMed-Medline was performed. The case was a 96-year-old woman who had taken alendronate. Intraoral clinical examination demonstrated hypersalivation and macrocheilia of the lower lip, associated with an ill-defined ulcer with erythematous borders measuring 20 mm in greatest diameter and covered with serofibrinous exudates. The aging of the population in developed and developing countries has increased the use of alendronate sodium to prevent osteoporosis and clinicians should be aware of possible oral adverse events associated with this drug. Key words:Adverse events, erythema multiforme, therapeutics, diagnosis, alendronate.

The canalis sinuosus is a neurovascular canal, a branch of nerve of infraorbital canal, through which the anterior superior alveolar nerve passes and then leans medially in course between the nasal cavity and the maxillary sinus, reaching the premaxilla in the canine and incisor region. The purpose of this article is to report a case with the presence of canalis sinuosus, in order to alert and guide professionals and discuss the morphology of this anatomical variation avoiding trans- and postsurgical disorders in dental implants. A 51-year-old female was attended to in a radiology clinic, reporting paresthesia in the right upper lip region and painful symptomatology after the installation of an implant in the corresponding region. The case revealed the presence of canalis sinuosus in imaging exams. The knowledge of this anatomical variation is essential for professionals, because attention to this region prevents irreversible damage. Therefore, the use of imaging examinations is recommended during the planning stages and treatment and after surgery in patients undergoing surgery in this area.

Congenital erythropoietic porphyria is a rare autosomal recessive disease produced by deficient activity of uroporphyrinogen III synthase, the fourth enzyme in the heme biosynthetic pathway. The disease impacts many organs, can be life-threatening and currently lacks curative treatments. Inherited mutations most commonly reduce the enzyme's stability, altering its homeostasis and ultimately blunting intracellular heme production. This results in uroporphyrin by-product accumulation in the body, aggravating associated pathological symptoms such as skin photosensitivity and disfiguring phototoxic cutaneous lesions. Here we demonstrated that the synthetic marketed antifungal ciclopirox binds to the enzyme, stabilizing it. Ciclopirox targeted the enzyme at an allosteric site distant from the active center and did not affect the enzyme's catalytic role. The drug restored enzymatic activity in vitro and ex vivo, and was able to alleviate most clinical symptoms of congenital erythropoietic porphyria in a genetic mouse model of the disease at sub-toxic concentrations. Our findings establish a possible line of therapeutic intervention against congenital erythropoietic porphyria which is potentially applicable to the majority of deleterious missense mutations causing this devastating disease.

Objective This study describes 9 cases of myiasis affecting the head and neck region and discusses the demographic distribution, treatment, clinical characteristics, and sequelae of the disease in light of the literature. Study Design The study was performed in 2 steps. In the first part, 9 cases seen over a period of 10 years at the Emergency Department of Hospital da Restauracao in Brazil were studied. In the second part, a literature search was performed in PubMed for articles on head and neck myiasis published from 1975 to March 2017. Results The case series mainly consisted of male patients in their 30s. The palate was the most commonly affected site. Myiasis was caused by Cochliomyia hominivorax in all patients, who were treated by mechanical removal of the larvae and debridement of necrotic tissue, followed by oral ivermectin. All patients had sequelae resulting from bone destruction. Conclusions Head and neck myiasis generally affects individuals with poor hygiene habits, drug users, and individuals with neurologic and psychosocial disorders. The treatment of choice is mechanical removal of larvae and surgical debridement combined with oral ivermectin. This study provides information that could help clinicians in the diagnosis and management of this condition.

Congenital erythropoietic porphyria (CEP) is an inborn error of heme biosynthesis characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in deleterious porphyrin accumulation in blood cells responsible for hemolytic anemia and cutaneous photosensitivity. We analyzed here the molecular basis of UROS impairment associated with twenty nine UROS missense mutations actually described in CEP patients. Using a computational and biophysical joint approach we predicted that most disease-causing mutations would affect UROS folding and stability. Through the analysis of enhanced green fluorescent protein-tagged versions of UROS enzyme we experimentally confirmed these data and showed that thermodynamic instability and premature protein degradation is a major mechanism accounting for the enzymatic deficiency associated with twenty UROS mutants in human cells. Since the intracellular loss in protein homeostasis is in excellent agreement with the in vitro destabilization, we used molecular dynamic simulation to rely structural 3D modification with UROS disability. We found that destabilizing mutations could be clustered within three types of mechanism according to side chain rearrangements or contact alterations within the pathogenic UROS enzyme so that the severity degree correlated with cellular protein instability. Furthermore, proteasome inhibition using bortezomib, a clinically available drug, significantly enhanced proteostasis of each unstable UROS mutant. Finally, we show evidence that abnormal protein homeostasis is a prevalent mechanism responsible for UROS deficiency and that modulators of UROS proteolysis such as proteasome inhibitors or chemical chaperones may represent an attractive therapeutic option to reduce porphyrin accumulation and prevent skin photosensitivity in CEP patients when the genotype includes a missense variant.