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SUMMARYThe metabolic conditions that prevail during bacterial growth have evolved with the faithful operation of repair systems that recognize and eliminate DNA lesions caused by intracellular and exogenous agents. This idea is supported by the low rate of spontaneous mutations (10-9) that occur in replicating cells, maintaining genome integrity. In contrast, when growth and/or replication cease, bacteria frequently process DNA lesions in an error-prone manner. DNA repairs provide cells with the tools needed for maintaining homeostasis during stressful conditions and depend on the developmental context in which repair events occur. Thus, different physiological scenarios can be anticipated. In nutritionally stressed bacteria, different components of the base excision repair pathway may process damaged DNA in an error-prone approach, promoting genetic variability. Interestingly, suppressing the mismatch repair machinery and activating specific DNA glycosylases promote stationary-phase mutations. Current evidence also suggests that in resting cells, coupling repair processes to actively transcribed genes may promote multiple genetic transactions that are advantageous for stressed cells. DNA repair during sporulation is of interest as a model to understand how transcriptional processes influence the formation of mutations in conditions where replication is halted. Current reports indicate that transcriptional coupling repair-dependent and -independent processes operate in differentiating cells to process spontaneous and induced DNA damage and that error-prone synthesis of DNA is involved in these events. These and other noncanonical ways of DNA repair that contribute to mutagenesis, survival, and evolution are reviewed in this manuscript.

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Pseudomonas aeruginosa is a high-priority bacterial agent that causes healthcare-acquired infections (HAIs), which often leads to serious infections and poor prognosis in vulnerable patients. Its increasing resistance to antimicrobials, associated with SPM production, is a case of public health concern. Therefore, this study aims to determine the antimicrobial resistance, virulence, and genotyping features of P. aeruginosa strains producing SPM-1 in the Northern region of Brazil. To determine the presence of virulence and resistance genes, the PCR technique was used. For the susceptibility profile of antimicrobials, the Kirby-Bauer disk diffusion method was performed on Mueller-Hinton agar. The MLST technique was used to define the ST of the isolates. The exoS+/exoU- virulotype was standard for all strains, with the aprA, lasA, toxA, exoS, exoT, and exoY genes as the most prevalent. All the isolates showed an MDR or XDR profile against the six classes of antimicrobials tested. HRC ST277 played a major role in spreading the SPM-1-producing P. aeruginosa strains.

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BACKGROUND: The control of the center of mass is essential for a stable and efficient gait. Post-stroke patients present several impairments, which may compromise the control of the center of mass during gait in the sagittal and frontal planes. This study aimed to identify changes in the vertical and mediolateral behavior of the center of mass during the single stance phase of post-stroke patients using the statistical parametric mapping analysis. It also aimed to identify alterations in the center of mass trajectories regarding the motor recovery stages. METHODS: Seventeen stroke patients and 11 neurologically intact individuals were analyzed. The statistical parametric mapping approach was used to identify changes in the center of mass trajectories between stroke and healthy groups. The trajectories of the center of mass of post-stroke individuals were compared according to their motor recovery status. FINDINGS: A near-flat vertical trajectory of the center of mass was indenfitifed in the stroke group compared to their healthy counterparts, especially on the paretic side. The center of mass trajectories in both directions (vertical and mediolateral) presented substantial alteration at the end of the single stance phase in the stroke group. The trajectory of the center of mass of the stroke group was symmetrical in the mediolateral direction between the sides. The trajectories of the center of mass presented similar pattern irrespective of the motor recovery status. INTERPRETATION: The statistical parametric mapping approach showed to be suitable for determining gait changes in post-stroke individuals, irrespective of their motor recovery stage.

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ABSTRACT Positron emission tomography (PET) is a non-invasive nuclear imaging technique that uses radiotracers to track cell activity. The radiopharmaceutical 18F-fluoro-2-deoxyglucose ([18F] FDG) is most commonly used in nuclear medicine for the diagnosis of various diseases, including stroke. A stroke is a serious condition with high mortality and morbidity rates. Rosmarinic acid (RA) is a promising therapeutic agent that exerts neuroprotective effects against various neurological diseases. Therefore, this study aimed to evaluate the applicability of [18F]FDG/PET for investigating the neuroprotective effects of RA in case of a global stroke model in mice. The [18F]FDG/PET technique facilitates the observation of ischemia and reperfusion injuries in the brain. Moreover, the recovery of glucose metabolism in three specific brain regions, the striatum, superior colliculus, and inferior colliculus, was observed after preconditioning with RA. It was concluded that the [18F]FDG/PET technique may be useful for stroke diagnosis and the assessment of treatment response. In addition, a long-term longitudinal study using biochemical analysis in conjunction with functional imaging may provide further conclusive results regarding the effect of RA on cerebral ischemia.

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BACKGROUND: Prefabricated and customized insoles are used in clinical practice to reduce foot pronation. Although data exist on the effects at key points within the stance phase, exploring the impact of different insoles using time series analysis may reveal more detail about their efficacy. RESEARCH QUESTION: What are the effects revealed by a time series analysis of arch-supported prefabricated insoles (PREFABRICATED) versus arch-supported prefabricated insoles customized with a 6º medial wedge (CUSTOMIZED) on the lower limb biomechanics during walking, stepping up and down tasks in individuals with pronated feet? METHODS: Nineteen individuals with excessive foot pronation performed walking, stepping up and down tasks using three insoles: CONTROL (flat insole), CUSTOMIZED, and PREFABRICATED. Angles and moments of ankle and knee coronal and hip transverse planes were compared between conditions using statistical parametric mapping (SPM). RESULTS: For walking, CUSTOMIZED reduced ankle eversion moment compared to CONTROL during midstance and PREFABRICATED during propulsion. CUSTOMIZED decreased KAM during midstance and propulsion compared to PREFABRICATED. Compared to CONTROL, CUSTOMIZED and PREFABRICATED reduced hip internal rotation during propulsion and loading response, respectively. CUSTOMIZED decreased eversion movement during midstance and propulsion for the stepping up task. PREFABRICATED reduced eversion movement during midstance in comparison to CONTROL. For the stepping down task, CUSTOMIZED increased eversion movement during propulsion compared to PREFABRICATED. CUSTOMIZED reduced hip internal rotation angle for stepping up task during propulsion, decreased medial rotation movement during midstance compared to CONTROL, and reduced medial rotation during midstance compared to PREFABRICATED. CUSTOMIZED increased KAM for stepping up and down tasks during propulsion. SIGNIFICANCE: These findings suggest that both CUSTOMIZED and PREFABRICATED reduce foot pronation. However, non-local effects, such as changes in KAM and hip internal rotation, were seen only in the CUSTOMIZED. Therefore, CUSTOMIZED may be preferable if the objective is to modify the knee and hip mechanics.

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The high rates of carbapenem resistance among Brazilian Pseudomonas aeruginosa isolates are mainly associated with the clone ST277 producing the carbapenemase SPM-1. Here, the complete genetic composition of a IncP plasmid harboring blaKPC-2 in isolates of this endemic clone carrying chromosomal blaSPM-1 was described using whole genome sequencing. These results confirm the association of these two carbapenemases in ST277 and also describe the genetic composition of a novel blaKPC-2-plasmid. Considering the fact that this association occurs in a high-risk clone, monitoring the dissemination of this plasmid should be a public health concern.

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Resumen Las enzimas VIM, IMP, y NDM son carbapenemasas de tipo metalo-beta-lactamasas (MBLs) que se encuentran ampliamente distribuidas en el mundo. La SPM-1 (Sao Paulo metalo-beta-lactamasa) es una MBL que fue descrita en Pseudomonas aeruginosa en Sao Paulo (Brasil) en 2002. Comunicamos por primera vez la presencia de SPM-1 en Chile, en un aislado de P aeruginosa resistente a meropenem e imipenem, detectado en un cultivo rectal de vigilancia de carbapenemasas desde un paciente internado en nuestra institución. La secuencia del producto de la RPC fue 100% idéntica a la secuencia de SPM-1 reportada en Brasil. El paciente tenía antecedentes de una angioplastía realizada en Brasil en 2004-2005. Como consecuencia de este hallazgo, la detección de SPM mediante RPC será incorporada a la búsqueda de rutina de carbapenemasas en P aeruginosa.

Abstract VIM, IMP, and NDM carbapenemases are metallo-beta-lactamases (MBLs) that are widely distributed throughout the world. SPM-1 (Sao Paulo metallo-beta-lactamase) is an MBL that was described in Pseudomonas aeruginosa in Sao Paulo (Brazil) in 2002. We report for the first time the presence of SPM-1 in Chile, in an isolate of P aeruginosa resistant to meropenem and imipenem, detected in a carbapenemase surveillance rectal swab culture, in a patient admitted to our institution. The sequence of the PCR product was 100% identical to the sequence of SPM-1 reported in Brazil. The patient had a history of an angioplasty performed in Brazil in 2004-2005. As a consequence of this finding, the detection of SPM by PCR will be incorporated into the routine screening for carbapenemases in P aeruginosa.

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BACKGROUND: Gastric carcinoma (GC) with second primary malignancy (SPM) is the most frequent combination within the multiple primary malignancies (MPM) group. The presentation of a GC associated with a synchronized SPM in the kidney is extremely rare and unusual. This study presents a rare case of synchronous tumors, describes the main associated risk factors, and emphasizes the need to rule out SPM. MAIN BODY: We present the case of a 63-year-old Hispanic woman with a history of smoking, weight loss, and gastrointestinal (GI) bleeding. GC was diagnosed by endoscopy, and during her workup for metastatic disease, a synchronous SPM was noted in the left kidney. The patient underwent resection of both tumors with a satisfactory postoperative course. A systematic review of the literature was performed using the Medline/PubMed, Science Direct, Scopus, and Google Scholar databases. A search of the literature yielded 13 relevant articles, in which the following main risk factors were reported: the treatment utilized, the grade and clinical stage, histopathological report, and in some cases survival. It is concluded that advanced age (> 60 years) and smoking are the main associated risk factors. CONCLUSION: Gastric carcinoma is the second most frequent neoplasm of the GI tract and the main neoplasm that presents a SPM. MPM screening is recommended in patients with gastric cancer. The clinical discovery of MPM of renal origin is rare and hence the importance of the current report.

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Introduction: Subtraction of ictal-interictal SPECT co-registered to MRI (SISCOM) is a quantification tool that can improve the sensitivity and specificity of the epileptogenic zone (EZ) localization. Commercially available image analysis software packages for SISCOM are costly, and Statistical Parametric Mapping (SPM) could be an alternative free software for the definition of the EZ. There are only a few studies that compare SISCOM using SPM (SISCOM-SPM) with visual analysis. Aim: To compare SISCOM-SPM vs. visual analysis for localization of the EZ in patients with pharmacoresistant focal epilepsies. Materials and methods: We evaluated all our patients with focal epilepsies that underwent ictal and interictal SPECT. We defined the reference standard to locate the EZ by pathology and follow-up (in patients submitted to surgery), or seizure semiology, serial EEG, long-term video-EEG, 18F-FDG PET/CT, and MRI (in patients who were not operated). We compared the location of the EZ by visual analysis of SPECT images and by SISCOM-SPM to the reference standard and classified as concordant, discordant, or partially concordant. Results: We included 23 patients. Visual analysis was concordant with the EZ reference standard in only 13 patients (56.5%), while SISCOM-SPM was concordant in 18 cases (78.3%), providing a 21.8% increase in the location of EZ. However, this difference was not significant due to the small sample size (p = 0.0856). Conclusion: Our preliminary results demonstrate that, in clinical practice, SISCOM-SPM has the potential to add information that might help localize the EZ compared to visual analysis. SISCOM-SPM has a lower cost than other commercially available SISCOM software packages, which is an advantage for developing countries. Studies with more patients are necessary to confirm our findings.

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The ability to create materials with improved properties upon transformation processes applied to conventional materials is the keystone of materials science. Here, hexagonal boron nitride (h-BN), a large-band-gap insulator, is transformed into a conductive two-dimensional (2D) material- bonitrol-that is stable at ambient conditions. The process, which requires compression of at least two h-BN layers and hydroxyl ions, is characterized via scanning probe microscopy experiments and ab initio calculations. This material and its creation mechanism represent an additional strategy for the transformation of known 2D materials into artificial advanced materials with exceptional properties.

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The worldwide dispersion and sudden emergence of new antibiotic resistance genes (ARGs) determined the need in uncovering which environment participate most as their source and reservoir. ARGs closely related to those currently found in human pathogens occur in the resistome of anthropogenic impacted environments. However, the role of pristine environment as the origin and source of ARGs remains underexplored and controversy, particularly, the marine environments represented by the oceans. Here, due to the ocean nature, we hypothesized that the resistome of this pristine/low-impacted marine environment is represented by distant ARG homologs. To test this hypothesis we performed an in silico analysis on the Global Ocean Sampling (GOS) metagenomic project dataset focusing on the metallo-ß-lactamases (MßLs) as the ARG model. MßLs have been a challenge to public health, since they hydrolyze the carbapenems, one of the last therapeutic choice in clinics. Using Hidden Markov Model (HMM) profiles, we were successful in identifying a high diversity of distant MßL homologs, related to the B1, B2, and B3 subclasses. The majority of them were distributed across the Atlantic, Indian, and Pacific Oceans being related to the chromosomally encoded MßL GOB present in Elizabethkingia genus. It was observed only a reduced number of metagenomic sequence homologs related to the acquired MßL enzymes (VIM, SPM-1, and AIM-1) that currently have impact in clinics. Therefore, low antibiotic impacted marine environment, as the ocean, are unlikely the source of ARGs that have been causing enormous threat to the public health.

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Metallo-ß-lactamases (MBLs) are the major group of carbapenemases produced by bacterial pathogens. The design of MBL inhibitors has been limited by, among other issues, incomplete knowledge about how these enzymes modulate substrate recognition. While most MBLs are broad-spectrum enzymes, B2 MBLs are exclusive carbapenemases. This narrower substrate profile has been attributed to a sequence insertion present in B2 enzymes that limits accessibility to the active site. In this work, we evaluate the role of sequence insertions naturally occurring in the B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1. We engineered a chimeric protein in which the sequence insertion of SPM-1 was replaced by the one present in Sfh-I. The chimeric variant is a selective cephalosporinase, revealing that the substrate profile of MBLs can be further tuned depending on the protein context. These results also show that the stable scaffold of MBLs allows a modular engineering much richer than the one observed in nature.

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Abstract: Metallo-beta-lactamase production is an important mechanism for carbapenem resistance of Pseudomonas aeruginosa , which represents an emerging public health challenge. We report the case of a patient admitted to an intensive care unit, with sepsis caused by multidrug-resistant São Paulo Metallo-beta-lactamase-1-producing P. aeruginosa . This is the first case of infection by this pathogenic strain in the State of Mato Grosso do Sul, Brazil. Thus, infection control measures are required for preventing future spread and outbreaks.

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BACKGROUND: Infections caused by multidrug resistant microorganisms are a global health problem, and Pseudomonas aeruginosa is an important nosocomial pathogen, easily disseminated in the hospital environment. The aim of this study was to determine SPM-1 in P. aeruginosa strains in 30 Brazilian hospitals and the genetic similarity of isolates. METHODS: We analyzed 161 isolates of carbapenem-resistant P. aeruginosa. Imipenem/EDTA and imipenem strip were used for phenotypic detection of MBL production; and real-time polymerase chain reaction (PCR) for genetic detection. Genetic similarity was determined by rep-PCR. RESULTS: We obtained 136/161 (84.5%) isolates with positive phenotypic result for metallo-ß-lactamase (MBL) and the blaSPM-1 gene was identified in 41 isolates. There was a predominant profile (>95% of genetic similarity) in 92.7% of isolates. This predominant profile was widely disseminated in Paraná state. CONCLUSION: SPM-1 is the main MBL identified in carbapenem-resistant P. aeruginosa in Southern Brazil. The genetic similarity among some isolates suggests a clonal expansion.

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A resistência bacteriana a antibióticos é um grave e crescente problema de saúde pública de âmbito mundial. O principal, e mais eficiente, mecanismo de resistência aos ß-lactâmicos em bacilos Gram-negativos é a produção de ß-lactamases, que possuem a capacidade de hidrolisar o anel ß-lactâmicos e consequentemente inativar essa classe de antibióticos. Vale ressaltar, que atualmente os antibióticos ß-lactâmicos são os mais utilizados clinicamente, particularmente em infecções graves. Dentre as ß-lactamases existentes destacam-se as carbapenemases, enzimas capazes de inativar a maioria dos antibióticos ß-lactâmicos. Uma grande preocupação é o fato dessas enzimas, em sua maioria, serem codificadas por plasmídeos, o que propicia a disseminação desses genes de resistência; portanto, é de extrema importância a realização de um rápido e efetivo monitoramento da presença de patógenos portadores desses genes de resistência, para que assim se possa prevenir a disseminação desses determinantes. Foram incluídos neste estudo 230 amostras únicas de Acinetobacter e Pseudomonas aeruginosa resistentes a imipenem detectados em pacientes internados em hospitais privados da cidade de São Paulo durante o período de fevereiro a outubro de 2013. As amostras foram avaliadas quanto à hidrólise de imipenem por espectrofotometria, quanto à presença de genes de carbapenemases por PCR e sequenciamento, e quanto à clonalidade por eletroforese em campos pulsados (PFGE) ou ERIC-PCR. Foram realizados ensaios de conjugação, transformação e sequenciamento completo de plasmídeos. Dentre as amostras de Acinetobacter spp. 80% (88) foram capazes de hidrolisar o imipenem. Dentre esses 76,1% (67) foram positivos para blaOXA-51-like, 19,3% (17) foram positivos para blaOXA-72. blaOXA-23, blaOXA-482 e blaIMP-1 foram detectados isoladamente em isolados distintos. O gene blaIMP-1 foi detectado em A. ursingii inserido em integron de classe 1 e representa a primeira descrição no Brasil. Uma nova carbapenemase OXA-482-like foi detectada em A. baumanii. Utilizando-se ERIC-PCR, observou-se uma grande diversidade de grupos clonais, com o máximo de quatro isolados por grupo. Dentre as amostras de P. aeruginosa, apenas 35,3% foram capazes de hidrolisar o imipenem. Dessas amostras, 14 possuíam o gene blaSPM-1, e isolados únicos possuíam, individualmente, os genes blaIMP, blaVIM, blaKPC-2 ou blaGES-23. O gene blaKPC-2 foi detectado inserido em contexto genético diferente dos descritos anteriormente, em plasmídeo IncU de 32 Kb, mobilizável, mas não conjugativo. Esta é a primeira descrição da sequencia completa de plasmídeo albergando o gene blaKPC-2 em P. aeruginosa no Brasil. Nas demais amostras (20) com atividade hidrolítica, não foram detectados genes de carbapenemase conhecidos, o que sugere a presença de genes de carbapenemase ainda não descritos. Em três amostras foi possível obter transformantes com plasmídeos, resistentes a carbapenêmicos. As amostras com blaSPM-1 apresentaram perfis de PFGE estreitamente relacionados. Em contraste, os perfis de PFGE das amostras com potenciais novas carbapenemases apresentaram índice de similaridade de Dice inferior ix a 80%, evidenciando grande diversidade clonal. Nossos achados evidenciam que a carbapenemase não intrínseca predominante em Acinetobacterem hospitais privados da cidade de São Paulo é OXA-72, e em hospitais privados há uma grande diversidade clonal. Em P. aeruginosa, a carbapenemase predominante é SPM-1, cuja disseminação é mediada por um único clone. Há potencialmente um número significativo de novas carbapenemases em Acinetobacter e P. aeruginosa, algumas delas mediadas por plasmídeos

Bacterial resistance to antibiotics is a serious and growing public health problem worldwide. The main and most efficient mechanism of resistance to ß-lactams in Gram-negative bacilli is the production of ß-lactamases, which have the ability to hydrolyze the ß-lactam ring and consequently inactivate this class of antibiotics. It is worth mentioning that currently ß-lactam antibiotics are the most used clinically, particularly in severe infections. Among the existing ß-lactamases, carbapenemases are capable of inactivating most ß-lactam antibiotics. A major concern is that these enzymes are mostly encoded by plasmids, which facilitates the spread of these resistance genes; therefore, it is of extreme importance to carry out a rapid and effective monitoring of the presence of pathogens bearing these resistance genes, in order to prevent the dissemination of these determinants. This study included 230 unique samples of imipenem-resistant Acinetobacterand Pseudomonas aeruginosa detected in patients hospitalized in private hospitals in the city of São Paulo during the period from February to October 2013. The samples were evaluated for the imipenem hydrolysis by spectrophotometry, the presence of carbapenemase genes by PCR and sequencing, and concerning clonality by pulsed field electrophoresis (PFGE) or ERIC-PCR. Conjugation, transformation and complete sequencing of plasmids were performed. Among Acinetobacter spp. samples, 80% (88) were able to hydrolyze imipenem. Among these, 76.1% (67) were positive for blaOXA-51-like genes and 19.3% (17) were positive for blaOXA-72. The blaOXA-23, blaOXA-482 and blaIMP-1 genes were detected alone in distinct isolates. The blaIMP-1 gene was detected in A. ursingii inserted in class 1 integron and represents the first description in Brazil. A novel OXA-482-like carbapenemase was detected in A. baumanii. Using ERIC-PCR, a great diversity of clonal groups was observed, with a maximum of four isolates per group. Among P. aeruginosa samples, only 35.3% were able to hydrolyze imipenem. Of these samples, 14 had the blaSPM-1 gene, and single isolates individually possessed the blaIMP, blaVIM, blaKPC-2 or blaGES-23 genes. The blaKPC-2 gene was found inserted in a genetic context different from those described previously, in a mobilizable, but not conjugative, 32 Kb IncU plasmid. This is the first description of the complete nucleotide sequence of a plasmid harboring the blaKPC-2 gene in P. aeruginosa in Brazil. In the remaining samples (20) with hydrolytic activity, no known carbapenemase genes were detected, suggesting the presence of carbapenemase genes not yet described. In three samples it was possible to obtain transformants with plasmids, resistant to carbapenems. Samples with blaSPM-1 showed closely related PFGE profiles. In contrast, the PFGE profiles of the samples with potential new carbapenemases showed Dice similarity index lower than 80%, evidencing a great clonal diversity. Our findings show that the predominant non-intrinsic carbapenemase in Acinetobacter in the city of São Paulo is OXA-72, and in private hospitals there is great clonal diversity. In P. aeruginosa, the predominant carbapenemase is SPM-1, the spread of this enzyme is mediated by a single clone. There are potentially a significant number of new carbapenemases in Acinetobacter and P. aeruginosa, some of them plasmid mediated

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Carbapenem-resistance mechanisms are a challenge in the treatment of Pseudomonas aeruginosa infections. We investigated changes in P. aeruginosa carbapenem-resistance determinants over a time period of eight years after the emergence of São Paulo metallo-β-lactamase in a university hospital in Rio de Janeiro, Brazil. Patients admitted to the intensive care unit (ICU) were screened for P. aeruginosa colonisation and followed for the occurrence of infections from April 2007 to April 2008. The ICU environment was also sampled. Isolates were typed using random amplified polymorphic DNA, pulsed-field gel electrophoresis and multilocus sequence typing. Antimicrobial susceptibility was determined by disk diffusion and E-test, production of carbapenemases by a modified-CarbaNP test and presence of carbapenemase-encoding genes by polymerase chain reaction. Non-carbapenemase resistance mechanisms studied included efflux and AmpC overexpression by PAβN and cloxacillin susceptibility enhancement, respectively, as well as oprD mutations. From 472 P. aeruginosa clinical isolates (93 patients) and 17 isolates from the ICU environment, high genotypic diversity and several international clones were observed; one environment isolate belonged to the blaSPM-1 P. aeruginosa epidemic genotype. Among isolates from infections, 10 (29%) were carbapenem resistant: none produced carbapenemases, three exhibited all non-carbapenemase mechanisms studied, six presented a combination of two mechanisms, and one exclusively displayed oprD mutations. Carbapenem-resistant P. aeruginosa displayed a polyclonal profile after the SPM-1 epidemic genotype declined. This phenomenon is connected with blaSPM-1 P. aeruginosa replaced by other carbapenem-resistant pathogens.

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A Síndrome Pré-Menstrual (SPM) é um problema de saúde com elevada prevalência: cerca de 80% das mulheres apresentam sintomas pré-menstruais e um percentual menor padece de formas mais graves como a Síndrome Disfórica Pré-Menstrual (SDPM). A Homeopatia, um sistema médico complexo que considera as singularidades de cada mulher, constitui uma forma de tratamento individualizado de acordo com o princípio da semelhança. O presente trabalho tem o objetivo de conhecer sobre a Homeopatia como possibilidade terapêutica para mulheres portadoras da Síndrome Pré-Menstrual (SPM). O texto aborda as diferentes manifestações da síndrome pré-menstrual, sua compreensão, diagnóstico e tratamento, segundo a ótica do modelo alopático e da episteme homeopática. Da mesma forma, descreve características de alguns medicamentos homeopáticos e discorre sobre pesquisas realizadas a respeito da eficácia ou efetividade da Homeopatia no tratamento da SPM. Trata-se de um estudo de revisão bibliográfica conduzido entre junho de 2015 e fevereiro de 2016. Houve consulta a diferentes fontes, tais como: matérias médicas homeopáticas, repertórios homeopáticos, artigos de revisão bibliográfica, artigos sobre pesquisas científicas, livros especializados e outras. A investigação realizada orientou a escolha de oito medicamentos homeopáticos com o potencial de tratar sintomas pré-menstruais, a saber: Sepia officinalis, Natrum muriaticum, Lachesis mutus, Pulsatilla nigricans, Nux vomica, Calcarea carbonica, Lycopodium clavatum e Folliculinum. Foram, também, encontrados quatorze artigos em periódicos científicos relacionados com o tema, entre esses ­ três revisões sistemáticas, cinco ensaios clínicos explanatórios e seis pesquisas com outros delineamentos. Alguns estudos indicaram que os medicamentos homeopáticos, inclusive os citados, podem aliviar sintomas da SPM e propiciar certo conforto às mulheres portadoras da síndrome. Os resultados dessas pesquisas parecem promissores, mas não conclusivos, pois os estudos realizados até a presente data apresentam importantes falhas metodológicas e uma parcela deles não acata o princípio da individualização do tratamento, nem outros postulados da Homeopatia. Além disso, é possível que os ensaios clínicos experimentais, explanatórios, não representem o único meio de se estimar esses resultados. Estudos com aspectos pragmáticos, que avaliam a efetividade do tratamento homeopático em cenários próximos à prática cotidiana, também parecem válidos e podem complementar o modelo anterior. Pesquisas futuras com diferentes delineamentos e que respeitem os princípios homeopáticos devem ser realizadas, para se investigar as reais possibilidades da Homeopatia no tratamento da SPM.(AU)

Premenstrual Syndrome (PMS) is a health problem with high prevalence: about 80% of women experience premenstrual symptoms and a lower percentage suffers from severe forms of the syndrome such as Premenstrual Dysphoric Disorder (PMDD). Homeopathy, which is a complex medical system that takes into account the particularities of each woman, is a form of individualized treatment according to the similarity principle. This work aims at knowing about homeopathy as a therapeutic possibility for women that suffer from Premenstrual Syndrome (PMS). The paper discusses the different manifestations of premenstrual syndrome, its understanding, diagnosis and treatment from the viewpoint of allopathic model and homeopathic episteme. Similarly, this work describes characteristics of some homeopathic medicines and discusses about conducted research regarding the efficacy or effectiveness of Homeopathy for PMS treatment. It is a bibliographic review conducted between June 2015 and February 2016. Different sources were consulted, such as: homeopathic materia medica, homeopathic repertories, literature review articles, articles on scientific research, specialized books and others. The search guided the choice of eight homeopathic medicines with the potential to treat premenstrual symptoms, i.e., Sepia officinalis, Natrum muriaticum, Lachesis mutus, Pulsatilla nigricans, Nux vomica, Calcarea carbonica, Lycopodium clavatum and Folliculinum. Fourteen articles in scientific journals related to the topic were also found: three systematic reviews, five explanatory clinical trials and six research with other designs. Some studies have indicated that homeopathic medicines, including the aforementioned ones, can relieve PMS symptoms and provide some comfort to women with the syndrome. The results of this research look promising but they are not conclusive because the studies conducted until now present significant methodological flaws and a portion of them does not obey the principle of individualization of treatment and other postulates of Homeopathy. Moreover, it is possible that the experimental trials, explanatory, do not represent the only way to estimate these results. Studies with pragmatic aspects that evaluate the effectiveness of homeopathic treatment in scenarios similar to daily practice also seem valid and may complement the previous model. Future studies with different designs that follow the homeopathic principles must be performed in order to investigate the real possibilities of Homeopathy in the treatment of PMS.

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Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific functions. Although peritoneal macrophages are one of the best-studied macrophage populations, recently it was demonstrated the co-existence of two subsets in mouse peritoneal cavity (PerC), which exhibit distinct phenotypes, functions, and origins. These macrophage subsets have been classified, according to their morphology, as large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). LPMs, the most abundant subset under steady state conditions, express high levels of F4/80 and low levels of class II molecules of the major histocompatibility complex (MHC). LPMs appear to be originated from embryogenic precursors, and their maintenance in PerC is regulated by expression of specific transcription factors and tissue-derived signals. Conversely, SPMs, a minor subset in unstimulated PerC, have a F4/80(low)MHC-II(high) phenotype and are generated from bone-marrow-derived myeloid precursors. In response to infectious or inflammatory stimuli, the cellular composition of PerC is dramatically altered, where LPMs disappear and SPMs become the prevalent population together with their precursor, the inflammatory monocyte. SPMs appear to be the major source of inflammatory mediators in PerC during infection, whereas LPMs contribute for gut-associated lymphoid tissue-independent and retinoic acid-dependent IgA production by peritoneal B-1 cells. In the previous years, considerable efforts have been made to broaden our understanding of LPM and SPM origin, transcriptional regulation, and functional profile. This review addresses these issues, focusing on the impact of tissue-derived signals and external stimulation in the complex dynamics of peritoneal macrophage populations.

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Pseudomonas aeruginosa is an opportunistic human pathogen responsible for causing a huge variety of acute and chronic infections with significant levels of morbidity and mortality. Its success as a pathogen comes from its genetic/metabolic plasticity, intrinsic/acquired antimicrobial resistance, capacity to form biofilm and expression of numerous virulence factors. Herein, we have analyzed the genetic variability, antimicrobial susceptibility as well as the production of metallo-ß-lactamases (MBLs) and virulence attributes (elastase, pyocyanin and biofilm) in 96 strains of P. aeruginosa isolated from different anatomical sites of patients attended at Brazilian hospitals. Our results revealed a great genetic variability, in which 86 distinct RAPD types (89.6% of polymorphisms) were detected. Regarding the susceptibility profile, 48 strains (50%) were resistant to the antimicrobials, as follows: 22.92% to the three tested antibiotics, 12.5% to both imipenem and meropenem, 11.46% to ceftazidime only, 2.08% to imipenem only and 1.04% to both ceftazidime and meropenem. Out of the 34 clinical strains of P. aeruginosa resistant to both imipenem and meropenem, 25 (73.53%) were MBL producers by phenotypic method while 12 (35.29%) were PCR positive for the MBL gene SPM-1. All P. aeruginosa strains produced pyocyanin, elastase and biofilm, although in different levels. Some associations were demonstrated among the susceptibility and/or production of these virulence traits with the anatomical site of strain isolation. For instance, almost all strains isolated from urine (85.71%) were resistant to the three antibiotics, while the vast majority of strains isolated from rectum (95%) and mouth (66.67%) were susceptible to all tested antibiotics. Urine isolates produced the highest pyocyanin concentration (20.15±5.65 µg/ml), while strains isolated from pleural secretion and mouth produced elevated elastase activity (1441.43±303.08 FAU) and biofilm formation (OD590 0.676±0.32), respectively. Also, MBL-positive strains produced robust biofilm compared to MBL-negative strains. Collectively, the production of site-dependent virulence factors can be highlighted as potential therapeutic targets for the treatment of infections caused by heterogeneous and resistant strains of P. aeruginosa.

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