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The emergence of drug-resistant pathogenic microorganisms has become a public health concern, with demand for strategies to suppress their proliferation in healthcare facilities. The present study investigates the physicochemical and antimicrobial properties of carbon dots (CD-MR) derived from the methyl red azo dye. The morphological and structural analyses reveal that such carbon dots present a significant fraction of graphitic nitrogen in their structures, providing a wide emission range. Based on their low cytotoxicity against mammalian cells and tunable photoluminescence, these carbon dots are applied to bioimaging in vitro living cells. The possibility of using CD-MR to generate reactive oxygen species (ROS) is also analyzed, and a high singlet oxygen quantum efficiency is verified. Moreover, the antimicrobial activity of CD-MR is analyzed against pathogenic microorganisms Staphylococcus aureus , Candida albicans , and Cryptococcus neoformans . Kirby-Bauer susceptibility tests show that carbon dots synthesized from methyl red possess antimicrobial activity upon photoexcitation at 532 nm. The growth inhibition of C. neoformans from CD-MR photosensitization is investigated. Our results show that N-doped carbon dots synthesized from methyl red efficiently generate ROS and possess a strong antimicrobial activity against healthcare-relevant pathogens.

Bradykinin (BK) is a peptide hormone that plays a crucial role in blood pressure control, regulates inflammation in the human body, and has recently been implicated in the pathophysiology of COVID-19. In this study, we report a strategy for fabricating highly ordered 1D nanostructures of BK using DNA fragments as a template for self-assembly. We have combined synchrotron small-angle X-ray scattering and high-resolution microscopy to provide insights into the nanoscale structure of BK-DNA complexes, unveiling the formation of ordered nanofibrils. Fluorescence assays hint that BK is more efficient at displacing minor-groove binders in comparison with base-intercalant dyes, thus, suggesting that interaction with DNA strands is mediated by electrostatic attraction between cationic groups at BK and the high negative electron density of minor-grooves. Our data also revealed an intriguing finding that BK-DNA complexes can induce a limited uptake of nucleotides by HEK-293t cells, which is a feature that has not been previously reported for BK. Moreover, we observed that the complexes retained the native bioactivity of BK, including the ability to modulate Ca 2+ response into endothelial HUVEC cells. Overall, the findings presented here demonstrate a promising strategy for the fabrication of fibrillar structures of BK using DNA as a template, which keep bioactivity features of the native peptide and may have implications in the development of nanotherapeutics for hypertension and related disorders.

Chikungunya virus (CHIKV) has become a significant public health concern due to the increasing number of outbreaks worldwide and the associated comorbidities. Despite substantial efforts, there is no specific treatment or licensed vaccine against CHIKV to date. The E2 glycoprotein of CHIKV is a promising vaccine candidate as it is a major target of neutralizing antibodies during infection. In this study, we evaluated the immunogenicity of two DNA vaccines (a non-targeted and a dendritic cell-targeted vaccine) encoding a consensus sequence of E2 CHIKV and a recombinant protein (E2* CHIKV ). Mice were immunized with different homologous and heterologous DNAprime-E2* protein boost strategies, and the specific humoral and cellular immune responses were accessed. We found that mice immunized with heterologous non-targeted DNA prime- E2* CHIKV protein boost developed high levels of neutralizing antibodies, as well as specific IFN-γ producing cells and polyfunctional CD4 + and CD8 + T cells. We also identified 14 potential epitopes along the E2 CHIKV protein. Furthermore, immunization with recombinant E2* CHIKV combined with the adjuvant AS03 presented the highest humoral response with neutralizing capacity. Finally, we show that the heterologous prime-boost strategy with the non-targeted pVAX-E2 DNA vaccine as the prime followed by E2* protein + AS03 boost is a promising combination to elicit a broad humoral and cellular immune response. Together, our data highlights the importance of E2 CHIKV for the development of a CHIKV vaccine.

Background: The control of the COVID-19 pandemic has been a great challenge. Understanding the thoughts and beliefs underlying vaccine hesitancy can help in the formulation of public policies. The present study aimed to analyze the social representations of hesitant Brazilians about vaccination against COVID-19., Methods: Qualitative research guided by the Theory of Social Representations, carried out through an online survey among Brazilian adults living in Brazil. The data were analyzed using the IRaMuTeQ software., Results: Of the 173,178 respondents, 10,928 were hesitant and declared reasons for vaccination hesitation. The analysis generated three classes: mistrust of the vaccine and underestimation of the severity of the pandemic; (dis)information and distrust of political involvement; and fear of adverse reactions to COVID-19 vaccines., Conclusions: Social knowledge, presented by the representations apprehended in this study, demonstrates difficulty in discerning the reliability of information and a social imagination full of doubts and uncertainties. Understanding the internal dynamics of these groups, with their representations of the world, is important to propose policies and actions that echo and cause changes in the understanding of the role of immunization. It is essential to shed light on the sociological imagination so that gaps filled with false information can be dismantled and confronted with scientific knowledge accessible to the population.

Despite numerous efforts over the last three decades, nucleic acid-based therapeutics still lack delivery platforms in the clinical stage. Cell-penetrating peptides (CPPs) may offer solutions as potential delivery vectors. We have previously shown that designing a "kinked" structure in the peptide backbone resulted in a CPP with efficient in vitro transfection properties. Further optimization of the charge distribution in the C-terminal part of the peptide led to potent in vivo activity with the resultant CPP NickFect55 (NF55). Currently, the impact of the linker amino acid was further investigated in the CPP NF55, with the aim to discover potential transfection reagents for in vivo application. Taking into account the expression of the delivered reporter in the lung tissue of mice, and the cell transfection in the human lung adenocarcinoma cell line, the new peptides NF55-Dap and NF55-Dab* have a high potential for delivering nucleic acid-based therapeutics to treat lung associated diseases, such as adenocarcinoma.

Objective: This study aims to assess the trustworthiness of information sources, perception of clear information about the vaccine, and strategies to increase adherence to vaccination to provide managers with information that helps establish effective communication with the population about vaccination., Method: This is an online survey conducted between January 22 and 29, 2021, preceded by an Informed Consent, that aims to assess vaccine hesitancy, which corresponded to the first week of vaccination initiation to prevent COVID-19 in Brazil. Data were obtained from a questionnaire made available through a free platform and stored in Google Forms and later exported to the SPSS statistical package for analysis. The sample consisted of all questionnaires from participants who self-declared as age 18 or older, Brazilian, and residing in Brazil at the time of the survey. Incomplete records with more than 50% of blank items and duplicates were excluded. All categorical variables were analyzed from their absolute and relative frequencies. Multivariate logistic regression was performed to verify the relationship between dependent variables and independent variables., Results: The results show that trust in information sources diverges between hesitant and non-hesitant. They also showed that some participants show an overall distrust that seems to have deeper foundations than issues related only to the source of information. The high rejection of television and the WHO as sources of information among hesitant suggests that integrated actions with research institutes, public figures vaccinating, and religious leaders can help to combat vaccine hesitation. Two actors become particularly important in this dynamic, both for good and bad, and their anti-vaxxer behavior must be observed: the doctor and the Ministry of Health., Conclusion: This study contributes to gathering valuable information to help understand the behavior and thinking relevant to the adherence to vaccination recommendations., Competing Interests: No authors have competing interests., (Copyright: © 2023 Reis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This article aims to evaluate the completeness of the pregnant woman's card filling according to a model standardized by the Ministry of Health. Hospital based, nationwide, cross-sectional study conducted between 2011 and 2012, evaluated data from pregnant women's cards. Variables related to personal, obstetric history and current pregnancy data were used to assess completeness. We used the Kotelchuck index for quantitative evaluation. We analysed 6,577 cards, equivalent to 39% of the cards presented at the time of delivery. The mean completeness was overall "bad" in Brazil and macro-regions, except in the Southern region. Nationwide, the mean completion was "regular" for personal antecedents, "good" for obstetric history, and "bad" for fields related to the current pregnancy. Prenatal care was adequate for 58% of pregnant women. We observed a reduced use of the card recommended by the Ministry of Health and failures in the completeness of filling valuable information of the pregnant woman's card, related to the current pregnancy.

Peptide-based hydrogels have attracted much attention due to their extraordinary applications in biomedicine and offer an excellent mimic for the 3D microenvironment of the extracellular matrix. These hydrated matrices comprise fibrous networks held together by a delicate balance of intermolecular forces. Here, we investigate the hydrogelation behavior of a designed decapeptide containing a tetraleucine self-assembling backbone and fibronectin-related tripeptides near both ends of the strand. We have observed that this synthetic peptide can produce hydrogel matrices entrapping >99% wt/vol % water. Ultrastructural analyses combining atomic force microscopy, small-angle neutron scattering, and X-ray diffraction revealed that amyloid-like fibrils form cross-linked networks endowed with remarkable thermal stability, the structure of which is not disrupted up to temperatures >80 °C. We also examined the interaction of peptide hydrogels with either NIH3T3 mouse fibroblasts or HeLa cells and discovered that the matrices sustain cell viability and induce morphogenesis into grape-like cell spheroids. The results presented here show that this decapeptide is a remarkable building block to prepare highly stable scaffolds simultaneously endowed with high water retention capacity and the ability to instruct cell growth into tumor-like spheroids even in noncarcinoma lineages.

Peptiplexes are soft biomaterials formed through the noncovalent association between cell-penetrating peptides and nucleic acids. Although internalization often involves electrostatic anchoring followed by endocytosis, the mode of action of these transporters remains elusive in many cases, and proper understanding of mechanisms behind their penetrating capabilities necessarily entails structural data at the nanoscopic scale. In this chapter, we examine the structural landscape of peptiplexes, emphasizing the complex behavior of these polyelectrolyte self-assemblies and how supramolecular order impacts their translocation efficiency. We discuss experimental tools commonly used to investigate the structure of peptiplexes and pay special attention to small-angle X-ray scattering (SAXS) as a suitable method for unveiling their nanoscale organization. A roadmap for standard SAXS measurements in CPP/DNA samples is presented alongside a selection of observations from our own experience dealing with SAXS applied to the investigation of CPPs., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The COVID-19 pandemic has affected the entire world, and the vaccine has emerged as a source of hope for return to normal life. Still, various countries have reported high vaccine hesitancy rates. It is important to know the vaccine hesitancy profile in Brazil to help design adequate communication strategies., Methods: A voluntary, anonymous online survey was conducted from January 22 to 29, 2021, including resident Brazilian adults to assess factors related to vaccine hesitancy. Sociodemographic and epidemiological data were analyzed. A bivariate analysis was conducted with the independent variables, with vaccine hesitancy as the outcome variable, and a multivariate logistic model was used to calculated adjusted odds ratios., Results: The sample included 173,178 respondents, and vaccine hesitancy was found in 10.5%. The principal factors associated with vaccine hesitancy were the following: assigning importance to the vaccinés efficacy (AOR = 16.39), fear of adverse reactions (AOR = 11.23), and assigning importance to the vaccinés country of origin (AOR = 3.72). Other risk factors were the following: male gender (AOR = 1.62), having children (AOR = 1.29), 9 years of schooling or less (AOR = 1.31), living in the Central-West region (AOR = 1.19), age ≥ 40 years (AOR = 1.17), and monthly income < U$788.68 (AOR = 1.13). The two vaccines available in Brazil, Covishield and CoronaVac, showed similar confidence, 80.13% and 76.36%, respectively, despite the higher rejection of the latter vaccinés Chinese origin., Interpretation: This online survey confirms the low vaccine hesitancy rate among Brazilians and allowed the identification of a profile that can assist the elaboration of communication strategies to increase vaccine adherence., Funding: National Institute of Women, Children and Adolescents Health Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brazil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Cell-penetrating peptides (CPPs) are a topical subject potentially exploitable for creating nanotherapeutics for the delivery of bioactive loads. These compounds are often classified into three major categories according to their physicochemical characteristics: cationic, amphiphilic, and hydrophobic. Among them, the group of hydrophobic CPPs has received increasing attention in recent years due to toxicity concerns posed by highly cationic CPPs. The hexapeptide PFVYLI (P, proline; F, phenylalanine; V, valine; Y, tyrosine; L, leucine; and I, isoleucine), a fragment derived from the C-terminal portion of α1-antitrypsin, is a prototypal example of hydrophobic CPP. This sequence shows reduced cytotoxicity and a capacity of nuclear localization, and its small size readily hints at its suitability as a building block to construct nanostructured materials. In this study, we examine the self-assembling properties of PFVYLI and investigate its ability to form noncovalent complexes with nucleic acids. By using a combination of biophysical tools including synchrotron small-angle X-ray scattering and atomic force microscopy-based infrared spectroscopy, we discovered that this CPP self-assembles into discrete nanofibrils with remarkable amyloidogenic features. Over the course of days, these fibrils coalesce into rodlike crystals that easily reach the micrometer range. Despite lacking cationic residues in the composition, PFVYLI forms noncovalent complexes with nucleic acids that retain β-sheet pairing found in amyloid aggregates. In vitro vectorization experiments performed with double-stranded DNA fragments indicate that complexes promote the internalization of nucleic acids, revealing that tropism toward cell membranes is preserved upon complexation. On the other hand, transfection assays with splice-correction oligonucleotides (SCOs) for luciferase expression show limited bioactivity across a narrow concentration window, suggesting that the propensity to form amyloidogenic aggregates may trigger endosomal entrapment. We anticipate that the findings presented here open perspectives for using this archetypical hydrophobic CPP in the fabrication of nanostructured scaffolds, which potentially integrate properties of amyloids and translocation capabilities of CPPs.

Efficient delivery of nanometric vectors complexed with nanoparticles at a target tissue without spreading to other tissues is one of the main challenges in gene therapy. One means to overcome this problem is to confine such vectors within microgels that can be placed in a target tissue to be released slowly and locally. Herein, a conventional optical microscope coupled to a common smartphone was employed to monitor the microfluidic production of monodisperse alginate microgels containing nanoparticles as a model for the encapsulation of vectors. Alginate microgels (1.2%) exhibited an average diameter of 125 ± 3 μm, which decreased to 106 ± 5 μm after encapsulating 30 nm fluorescent nanoparticles. The encapsulation efficiency was 70.9 ± 18.9%. In a 0.1 M NaCl solution, 55 ± 5% and 92 ± 4.7% of nanoparticles were released in 30 minutes and 48 hours, respectively. Microgel topography assessment by atomic force microscopy revealed that incorporation of nanoparticles into the alginate matrix changes the scaffold's interfacial morphology and induces crystallization with the appearance of oriented domains. The high encapsulation rate of nanoparticles, alongside their continuous release of nanoparticles over time, makes these microgels and the production unit a valuable system for vector encapsulation for gene therapy research., (© 2021 Wiley Periodicals LLC.)

Fermentative herbivorous animals have peculiar conformations of the digestive system. It is known that B. variegatus obtained the capacity for evolutionary adaptation, due to their ecology and eating habits. However, despite the literature on feeding management for this species, there is a lack of published information regarding its gastric morphology, and such information would support a better understanding on the diet and digestion of these individuals. We found seven gastric compartments, which histologically revealed three distinct patterns: an aglandular keratinized fraction (mechanical stomach) and two glandular fractions, one a mucus secretor and the other one composed of acid secreting cells (chemical stomach). With these evidences we understand that these individuals have gastric resemblance to ruminants, with some inherent peculiarities of this species, including the transit of the bolus., (© 2020 Wiley Periodicals LLC.)

Penetratin is a short Trojan peptide that attracts great interest in biomedical research for its capacity to translocate biological membranes. Herein, we study in detail both self-assembly and intracellular delivery of DNA by the heptamer KIWFQNR, a truncated peptide derived from Penetratin. This shortened sequence possesses a unique design with bolaamphiphilic characteristics that preserves the longest noncationic amino acid portion found in Penetratin. These features convey amphipathicity to assist self-assembly and make it a suitable model for exploring the role of hydrophobic residues for peptide interaction and cell uptake. We show that the fragment forms peptiplexes (i.e., peptide-DNA complexes), and aggregates into long nanofibers with clear β-sheet signature. The supramolecular structure of nanofibers is likely composed of DNA cores surrounded by a peptide shell to which the double helix behaves as a template and induces fibrillization. A nucleation and growth mechanism proceeding through liquid-liquid phase separation of coacervates is proposed for describing the self-assembly of peptiplexes. We also demonstrate that peptiplexes deliver double-stranded 200 bp DNA into HeLa cells, indicating its potential for preparing non-viral vectors for oligonucleotides through noncovalent strategies. Since the main structural features of native Penetratin are conserved in this simpler fragment, our findings also highlight the role of uncharged amino acids for structuration, and thus for the ability of Penetratin to cross cell membranes.

Amphiphilicity is the most critical parameter in the self-assembly of surfactant-like peptides (SLPs), regulating the way by which hydrophobic attraction holds peptides together. Its effects go beyond supramolecular assembly and may also trigger different cell responses of bioactive peptide-based nanostructures. Herein, we investigate the self-assembly and cellular effects of nanostructures based on isomeric SLPs composed by arginine (R) and phenylalanine (F). Two amphipathic designs were studied: a diblock construct F4R4 and its bolaamphiphile analog R2F4R2. A strong sequence-dependent polymorphism emerges with appearance of globules and vesicle-like assemblies, or flat nanotapes and cylindrical micelles. The diblock construct possesses good cell penetrating capabilities and effectiveness to kill SK-MEL-28 melanoma tumor cells, in contrast to reduced intracellular uptake and low cytotoxicity exhibited by the bolaamphiphilic form. Our findings demonstrate that amphipathic design is a relevant variable for self-assembling SLPs to modulate different cellular responses and may assist in optimizing the production of nanostructures based on arginine-enriched sequences in cell penetrating and antimicrobial peptides.

Three model arginine-rich tripeptides RXR (X = W, F or non-natural residue 2-napthylalanine) were investigated as antimicrobial agents, with a specific focus to target Pseudomonas aeruginosa through membrane lysis. Activity against biofilms was related to binding of the second messenger molecule, nucleotide bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP). Strong selective activity against P. aeruginosa in planktonic form was observed for RFR and RWR.

One of the most remarkable examples of cell-penetrating peptides (CPPs) is Penetratin , a 16-mer fragment derived from the Drosophila Antennapedia homeobox. Understanding the structure of Penetratin /DNA complexes is a key factor for the successful design of new vectors for gene delivery and may assist in optimizing molecular carriers based on CPPs. Herein, we present a comprehensive study on the nanoscale structure of noncovalent complexes formed between Penetratin and DNA. The strong cationic nature of the peptide makes it a very efficient agent for condensing DNA strands via electrostatic attraction, and we show for the first time that DNA condensation is accompanied by random-to-β-sheet transitions of Penetratin secondary structure, demonstrating that nucleic acids behave as a structuring agent upon complexation. For the first time, nanoscale-resolved spectroscopy is used to provide single-particle infrared data from DNA carriers based on CPPs, and they show that the structures are stabilized by Penetratin β-sheet cores, whereas larger DNA fractions are preferentially located in the periphery of aggregates. In-solution infrared assays indicate that phosphate diester groups are strongly affected upon DNA condensation, presumably as a consequence of charge delocalization induced by the proximity of cationic amide groups in Penetratin . The morphology is characterized by nanoassemblies with surface fractal features, and short-range order is found in the inner structure of the scaffolds. Interestingly, the formation of beads-on-a-string arrays is found, producing nanoscale architectures that resemble structures observed in early steps of chromatin condensation. A complexation pathway where DNA condensation and peptide pairing into β-sheets are key steps for organization is proposed.

Glutamic acid-rich peptides are crucial to a variety of biological processes, including glutamatergic neurotransmission and immunological defense. Glutamic acid sequences often exhibit unusual organization into β 2 -type sheets, where bifurcated H bonds formed between glutamic acid side chains and NH in amide bonds on adjacent β-strands play a paramount role for stabilizing the molecular assembly. Herein, we investigate the self-assembly and supramolecular structure of simplified models consisting of alternating glutamic acid/phenylalanine residues. Small-angle X-ray scattering and atomic force microscopy show that the aggregation pathway is characterized by the formation of small oligomers, followed by coalescence into nanofibrils and nanotapes. Amyloidogenic features are further demonstrated through fiber X-ray diffraction, which reveal molecular packing according to cross-β patterns, where β-strands appear perpendicularly oriented to the long axis of nanofibrils and nanotapes. Nanoscale infrared spectroscopy from individual nanoparticles on dried samples shows a remarkable decrease of β 2 -sheet content, accompanied by growth of standard β-sheet fractions, indicating a β 2 -to-β 1 transition as a consequence of the release of solvent from the interstices of peptide assemblies. Our findings highlight the key role played by water molecules in mediating H-bond formation in β 2 -sheets commonly found in amyloidogenic glutamic acid-rich aggregates., (© 2019 European Peptide Society and John Wiley & Sons, Ltd.)

Background: Chronic low-grade inflammation, combined with traditional cardiovascular risk factors, is common in obesity, providing systemic inflammation that is associated with increased cardiovascular risk. Studies have shown serum mieloperoxidase as a potential biomarker and its clinical applicability for evaluating cardiovascular risk. This study aimed to evaluate the MPO in obese individuals, with or without systemic inflammation and potential cardiovascular risk, as well as correlating MPO with some classic cardiovascular risk parameters., Methods: Inflammatory and cardiovascular risk markers, as well as different biochemical and hematological laboratory parameters, were analyzed. The volunteers were divided into 3 groups according to the presence (hs-CRP>3 mg/L) or absence (hs-CRP<3 mg/L) of systemic inflammation and possible cardiovascular risk., Results: MPO was significantly increased (p<0.05) in the obese individuals with systemic inflammation. A significant increase (p<0.05) in the following biochemical parameters: glucose, HbA1c, triglycerides, non-HDL, TG/HDL was observed, and a significant decrease (p<0.01) in HDL was observed. Significant increases in the counts of total leukocytes, neutrophils and monocytes (p<0.01), as well as elevated blood pressure (p<0.05), were observed in the group of obese individuals with systemic inflammation. Serum MPO levels were correlated with classic proinflammatory and cardiovascular risk parameters., Conclusions: High serum levels of MPO were observed in obese individuals with hs-CRP above 3 mg/L, which is a classic biomarker for inflammation and cardiovascular risk, suggesting the potential role of MPO in clinical applicability for cardiovascular disease in this population. However, considering that inflammation in obesity appears to manifest as a non-classical mechanism, further studies are necessary to elucidate the role of MPO in cardiovascular events in the population with obesity., (© Georg Thieme Verlag KG Stuttgart · New York.)

Candidemia is a frequent condition in Neonatal Intensive Care Units (NICU) and usually complicates the newborns clinical course. Several factors are responsible for candidiasis, such as prematurity and use of broad-spectrum antibiotics, and in these cases, there are the involvement of various Candida species, as C. albicans, and C. parapsilosis. However, other species as C. haemulonii has been rarely described in candidemia cases, being considered an emergent pathogen. Thus, we report a case of neonatal candidemia by C. haemulonii and a review of literature of fungemia by this yeast. The patient was a neonate with gestational age of 26 weeks and birth weight of 660 g hospitalized in a NICU from a Brazilian hospital. The identification of the etiological agent was performed by phenotypic methods, scanning electron microscopy, sequencing of the ITS region of rDNA, and mass spectrometry. Antifungal susceptibility testing was carried out according to the Clinical Laboratories and Standards Institute guidelines. The newborn was diagnosed with candidemia by C. haemulonii resistant to amphotericin B with minimal inhibitory concentration (MIC) of 8 µg/mL, sensitive to fluconazole (MIC: 8 µg/mL) and voriconazole (MIC: 0.12 µg/mL). The treatment with fluconazole (12 mg/kg/day) was established with good outcome. Candidemia by C. haemulonii is still being limited to a few sporadic cases in adults with endemic and restricted occurrences in neonates. Usually, the therapy with amphotericin B is ineffective against this species. Our results showed the importance of the mycological diagnosis associated to antifungigrama for the successful clinical management followed by important epidemiological data.

Objective: To produce a historical account of rehabilitation actions in the context of the Brazilian Unified Health Care System (SUS)., Methods: Search of SciELO, LILACS, and MEDLINE databases for literature published between 1980 and 2009. The following Portuguese search terms were used: Sistema Unico de Saúde, reabilitação, políticas de saúde, assistência médica, história. The English terms "rehabilitation" and "public health" were also used. Federal laws and Ministry of Health manuals available at the city of Rio de Janeiro Coordinating Office for Rehabilitation Programs, Fundação Instituto Oswaldo Cruz library, and in BIREME database were also surveyed., Results: Only a small number of publications were recovered (four books, three Health Ministry manuals, four articles published in Brazil, one master's thesis, and one doctoral dissertation). Nevertheless, analysis of these materials revealed that since many municipalities are still incapable of ensuring the right to universal and comprehensive health care, rehabilitation actions are often carried out in a precarious manner, unsupported by an adequate and comprehensive policy. On the other hand, there have been real improvements in terms of expanding care to the population with special needs., Conclusions: There still are factors hindering the achievement of optimal results in the care to people with special needs. The challenge of action planning must be undertaken especially by municipal governments to ensure an adequate supply of services and thus equity of access and comprehensive health care.

OBJECTIVE: To report a case of Devic disease, emphasizing its diagnosis, in addition to reviewing the medical literature. DESCRIPTION: Male, six-year-old patient suddenly developed weakness in lower limbs, with resolution during hospital stay. However, as the weakness disappeared, loss of vision occurred. The symptoms were reverted after the use of prednisone. COMMENTS: The diagnostic and therapeutic approach was similar to that used in other cases reported by different reference centers. In other words, clinical diagnosis and prednisone therapy were used, with the complete improvement of symptoms. However, there is still some controversy surrounding its etiology and relationship with other demyelinating diseases, such as multiple sclerosis.

Lyophilized cellulose was analysed to verify the degree of inflammatory reaction and axon realignment in the sciatic nerve after loss of neural substance. Ten mongrel dogs were divided into: Group 1 - 1 cm section of sciatic nerve which was replaced at lesion site; Group 2 nerve section without fragment replacement. The section site was involved with lyophilized cellulose. Group 3 -1 cm fragment section sutured epineurally. Motor response started at eighth week. Moderate fibrotic reaction to cellulose was seen in Group 1 and 2 animals. Groups 1 and 3 showed coaptation between the nerve and nerve graft with ongoing axons. In Group 2, 1 dog showed regrowth of axons through the empty space. It was concluded that lyophilized cellulose caused moderate fibrous reaction when implanted in peripheral nerve lesions with loss of substance; it can act as envelop protection in those lesions mainly if a neural graft is inserted.

Thoracic spine arachnoid ossification is a relatively rare disease that affects mainly women and causes sensory, motor, and sphinctal symptoms associated with inferior limb pain. Based on three cases, the authors comment on pathogenic and surgery-related aspects of the disease. The patient in Case 1 was followed over the course of 23 years. Spinal cavitation is highlighted in Case 2, and yellow, gross, half-ring ossification is described in Case 3. Calcium deposits usually occur in the middle and lower thoracic spine where the majority of trabeculated arachnoid cells are located. Operative treatment does not interrupt the ossification process, which continues over time, causing progressive deterioration in the patient. Spinal cavitation can occur due to spinal cord tethering, stretching, and central cord edema formation, accompanied by cerebrospinal fluid blockage and pulse pressure changes. The results of surgical intervention are poor, offering short-term recovery with later deterioration. Multiple pathogenic factors are involved in this clinical syndrome including metabolic changes.

Hemostatic effects of oxidized cellulose (Surgicel) are well known. Based on a possible similar effect of a sponge obtained after lyophilization of biosynthetic cellulose, two different experimental studies were planned. Phase I-Pieces of cellulose sponge were inserted into small provoked cortical wounds of twelve dogs. The time elapsed to obtain bloodstill after cortical damage and application of cellulose was observed in every dog, searching to detect any possible hemostatic effect of the material. The animals were sacrificed after 7, 30 and 90 days. An average time of 1 minute was elapsed until bleeding control was achieved. No clinical adverse effect was noticed. Microscopy showed histiocytic and mild foreign body reaction at 7 days, which diminished at 30 days. Almost no reaction surrounded the implant at 90 days. Lyophilized cellulose has a peculiar eosinophilic appearance, composed by thin irregular filaments which diminished their thickness with the time. At 90 days only sparse irregular cellulose filaments could be detected. Phase II-Small equal sponge fragments were inserted in the liver of twelve rats and observed 7, 30 and 90 days. At autopsy, small peritoneal adhesions were noticed at 30 and 90 days. Microscopy showed intense histioplasmocytic and foreign body reaction in all animals mainly at 7 days. In two animals, refringent intracellular cellulose particles were evident inside giant foreign body cells after 90 days. This fact evidences that cellulose can be reabsorbed by phagocytic phenomena when implanted in mammalians. A comparative group with other hemostatic material and the same method must be done to clarify the issue of hemostatic effects of this membrane.

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6% in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30% of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

In the search for a new synthetic substitute for the dura mater, the authors conducted a research study using 32 mongrel dogs divided into three groups. Group I animals (21 dogs) underwent a right-sided parietooccipital craniotomy and substitution of two 1-cm pieces of dura mater by two different grafts: one piece of biosynthetic cellulose (50 mu thick) and one fragment of temporal fascia. The animals were observed for 30, 90, or 180 days. Group II animals (five dogs) underwent a somewhat larger craniotomy, removal of a 2-cm piece of dura mater, and lesioning of the cortex made by a thin sharp forceps, which caused bleeding that was controlled by application of a thin film of cellulose (10 mu thick). Duraplasty was performed using a 50-mu-thick cellulose membrane to complete the procedure and the animals were observed over a period of 270 days. Group III animals (six dogs) underwent smaller (1-cm diameter) bilateral parietal craniectomy, which included additional covering of the dura on the left side with 50-mu-thick cellulose and a suture of temporalis muscle. This group was observed for 40, 60, 80, or 120 days. Transient mild clinical symptoms were observed during the early postoperative period. At autopsy, macroscopic examination demonstrated good acceptance of the grafts with few and moderate extradural fibrosis, which caused adherence of the implants to the bone fragment. No adherence to the cortex was observed. Microscopic examination demonstrated absence of graft adherence to the cortical surface even when the cortex was injured. The cellulose was enveloped by two layers of connective tissue, the external layer being thicker than the internal one. Cellulose fibers increased in thickness over time until 30 days and then decreased in thickness until 270 days. This decrease in thickness between 30 to 270 days was statistically significant (p < 0.05). The physical properties of biosynthetic cellulose and the low cellular reaction to its implantation qualify this material as a dural substitute. Additional long-term studies must be undertaken to complete this report.

A series of 129 patients harbouring extradural hematomas was analysed considering the neurological state immediately before operation as the most consistent variable. Seventy eight patients were considered to be comatose (Group I) and 51 were noncomatose. Among the comatose group, 30 were investigated with computerized tomography (23.3% mortality, 50% good results), 31 were submitted to angiography (48.3% mortality, 38.7% good results), and 17 were operated based on the neurological examination and skull radiography (47% mortality, 35.2% good results). The presence or absence of skull fracture and the density of hematoma did not change the final outcome. Associated intracranial lesions increased the mortality and lowered the good results in both groups. Frontal hematomas (10 cases) in the comatose group were associated with high mortality (52.6%) due to bad neurological state (Glasgow 3-5) and to isolated or multiple intracranial associated lesions (6 patients).

The authors report two cases of infantile metachromatic leucodystrophy in monozygotic female twins, born from a second cousin marriage (f = 1/32). The zygosity was determined by means of obstetrics and genetics marker findings.

Four cases of the occlusive arterial disease "moyamoya" type, are reported with comments on the clinical, roentgenological and embriological aspects. The clinical onset in all four cases was of isquemic type, in spite of different ages (2 adult male, one young adult female, 1 child female). Some particular symptoms are analysed, mainly the constant complaint of episodes in which the patient is, suddendly, extremely tired. The causes of this episodes are thought to be due to suddendly lowering of the cerebral perfusion in the disease. The importance of the radiological appearance is emphasyzed. The plain roentgenographic films, the site of the occlusion, the associated vascular malformations, the collateral circulation and the site of the vascular nest, are discussed. Some embriologic aspects of the etiology including the variable time onset of the pathologic process are also discussed.

The incidence of infection in neurological surgery is analysed by the author due to an almost epidemic occurrence of wound contamination by staphylococcus aureus in the year 1977. A brief review of the literature data is presented concerning the factors related to the patient's own immunity, the operative wound and the hospital environment, that may cause infection. Based on 733 operations done in a period of 50 months the author exposes the modifications installed for avoiding the infective sources. Antiseptic technic and surgical tactic were modified during the three steps of this study. In the first two periods, each of one lasting 17 months, the infection rates for clean surgical procedures were 10,3 and 6,7% respectively. By the last 15 months, when topical oxacyllin powder was added, the infection rate dropped to 0,6%. The general infection rates for clean, clean with implants, clean-contaminated and contaminated operations, during the three periods were 7,08, 6,8 and 3,4%. A critical review of the data concerning to systemic and topical prophylactic antibiotic therapy is followed by comments on the basis of the technical changes made in this clinical study. Shaving close to the operation, dry preparation of the scalp flap and muscle, use of only bipolar coagulation, restrict use of serum irrigation during the epidural stages of the operation an topical use of oxacillin powder before wound closure were the main technical modification introduced.

The comparative clinic-radiological study between 45 patients with spasmodic torticollis and the same amount of patients with either essential Parkinsonism or tremor is reported. The study was based mainly on the alterations verified by plain roentgenograms and pneumoencephalography. The comparison between the findings obtained on both groups led the authors to conclude that neuroradiological aspects have statiscally no value in clarifying the etiology of the spasmodic torticollis.

The case of a fronto-parietal parasagital "in plaque" meningioma which growed mainly in the subdural space is reported. The atipical angiographic picture of a subdural hematoma is described with comments on the mechanisms that occasioned this radiological appearance. The rarity of this finding and the need of angiographycal study of both internal and external carotid systems by the intracranial meningiomas are emphasized.