Reduced graphene oxide, but not carbon nanotubes, slows murine melanoma after thermal ablation using LED light in B16F10 lineage cells.

Photodynamic therapy is a minimally invasive health technology used to treat cancer and other non-malignant diseases, as well as inactivation of viruses, bacteria and fungi. In this work, we sought to combine the phototherapy technique using low intensity LED (660 nm) to induce ablation in melanoma tumor in mice treated with nanoparticles. In vitro and in vivo studies were conducted, and our results demonstrated that multi-walled carbon nanotubes (MWCNTs) do not destroy tumor cells in vivo, but stimulate the inflammatory process and angiogenesis. Reduced graphene oxide (rGO), has been shown to play a protective role associated with the LED ablation, inducing necrosis, stimulation of immune response by lymphoproliferation, and decreased tumor mass in vivo. We consider that LED alone can be very effective in controlling the growth of melanoma tumors and its association with rGO is potentiated.

Thiol-antioxidants interfere with assessing silver nanoparticle cytotoxicity.

Many studies have shown that silver nanoparticles (AgNP) induce oxidative stress, and it is commonly assumed that this is the main mechanism of AgNP cytotoxicity. Most of these studies rely on antioxidants to establish this cause-and-effect relationship; nevertheless, details on how these antioxidants interact with the AgNP are often overlooked. This work aimed to investigate the molecular mechanisms underlying the use of antioxidants with AgNP nanoparticles. Thus, we studied the molecular interaction between the thiol-antioxidants (N-acetyl-L-Cysteine, L-Cysteine, and glutathione) or non-thiol-antioxidants (Trolox) with chemically and biologically synthesized AgNP. Both antioxidants could mitigate ROS production in Huh-7 hepatocarcinoma cells, but only thiol-antioxidants could prevent the cytotoxic effect, directly binding to the AgNP leading to aggregation. Our findings show that data interpretation might not be straightforward when using thiol-antioxidants to study the interactions between metallic nanoparticles and cells. This artifact exemplifies potential pitfalls that could hinder the progress of nanotechnology and the understanding of the nanotoxicity mechanism.

Pradimicin-IRD from Amycolatopsis sp. IRD-009 and its antimicrobial and cytotoxic activities.

A new polycyclic antibiotic, pradimicin-IRD, was isolated from actinobacteria Amycolatopsis sp. IRD-009 recovered from soil of Brazilian rainforest undergoing restoration area. This molecule is the major compound produced in solid culture media. The new compound was detected by a focused method of precursor ion (high-performance liquid chromatography coupled to tandem mass spectrometer) developed previously to identify unusual aminoglycosyl sugar moieties. The compound was isolated and its structure was, therefore, elucidated by high-resolution mass spectrometry, and 1D and 2D nuclear magnetic resonance experiments. Pradimicin-IRD displayed potential antimicrobial activity against Streptococcus agalactiae (MIC 3.1 µg/mL), Pseudomonas aeruginosa (MIC 3.1 µg/mL) and Staphylococcus aureus (MIC 3.1 µg/mL), and also cytotoxicity against tumour and non-tumour cell lines with IC50 values ranging from 0.8 µM in HCT-116 colon carcinoma cells to 2.7 µM in MM 200 melanoma cells. Particularly, these biological properties are described for the first time for this chemical class.

Pressurized liquid extraction of flavanols and alkaloids from cocoa bean shell using ethanol as solvent.

Cocoa shell (CS) is a co-product of the cocoa industry used mainly as fuel for boilers but with secondary applications as fertilizer and in animal feed. Although it is known that this material is rich in flavanols and alkaloids, to date, a study has not been conducted that has quantitatively identified these compounds in CS. Thus, the aim of this work was to characterize CS in terms of its composition, regarding catechin, epicatechin, procyanidin B2, caffeine and theobromine, and to evaluate the extraction kinetics of the total flavanols using pressurized liquid extraction (PLE) with absolute ethanol. For the determination of the extraction kinetic data, the DMAC method was used, while each compound was quantified using a UPLC-MS/MS analysis. The major compounds found were theobromine and epicatechin (mean values of 9.89 and 3.5 mg/g CS, respectively). PLE proved to be quite effective; the flavanols extraction yield was enhanced by increasing the temperature and extraction time however, high extraction times and temperatures degraded the procyanidins B2. Peleg's model applied to extraction data description provided a reasonable agreement with the experimental results, which allows their application in modeling and optimization of solid-liquid extraction of the total flavanols from cocoa bean shell.

Anthocyanidins structural study using positive electrospray ionization triple quadrupole mass spectrometry and H/D exchange.

We report herein a detailed structural study by collision-induced dissociation (CID) of nonglycosylated anthocyanins (anthocyanidins) using electrospray ionization triple quadrupole mass spectrometry (ESI-QqQ) and isotope labeling experiments to understand the fragmentation process often used in mass spectrometry analysis of this class of compounds. Tandem mass spectrometric product ion spectra for three anthocyanidins (cyanidin, delphynidin, and pelargonin) were evaluated to propose fragmentation mechanisms to this natural colorant class of organic compounds. The proposed rearrangements, retro Diels-Alder reaction, water loss, CO losses, and stable acylium ion formation, were evaluated based on tandem mass spectrometric experiments of normal and labeled precursor ions together to computational thermochemistry. B3LYP/6-311 + G** ab initio calculations studies were carried out to obtain energy diagrams to show the viability of the proposed mechanisms. The CO losses fragmentation channels have lower energies when compared with water losses and the other proposed fragmentations. The isotope labeling experiments indicate the H/D exchange of the hydroxyl protons and corroborate the proposed general fragmentation mechanism for anthocyanidins.

Effects of intravesical therapy with platelet-rich plasma (PRP) and Bacillus Calmette-Guérin (BCG) in non-muscle invasive bladder cancer.

This study describes the effects of a promising therapeutic alternative for non-muscle invasive bladder cancer (NMIBC) based on Bacillus Calmette-Guerin (BCG) intravesical immunotherapy combined with Platelet-rich plasma (PRP) in an animal model. Furthermore, this study describes the possible mechanisms of this therapeutic combination involving Toll-like Receptors (TLRs) 2 and 4 signaling pathways. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea (MNU). After treatment with MNU, the animals were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU + PRP group, MNU + BCG group and MNU + PRP + BCG group. Our results demonstrated that PRP treatment alone or associated with BCG triggered significant cytotoxicity in bladder carcinoma cells (HTB-9). Animals treated with PRP associated to BCG clearly showed better histopathological recovery from the cancer state and decrease of urothelial neoplastic lesions progression in 70% of animals when compared to groups that received the same therapies administered singly. In addition, this therapeutic association led to distinct activation of immune system TLRs 2 and 4-mediated, resulting in increased MyD88, TRIF, IRF3, IFN-γ immunoreactivities. Taken together, the data obtained suggest that interferon signaling pathway activation by PRP treatment in combination with BCG immunotherapy may provide novel therapeutic approaches for non-muscle invasive bladder cancer.

Direct Analysis of Amphetamine Stimulants in a Whole Urine Sample by Atmospheric Solids Analysis Probe Tandem Mass Spectrometry.

Amphetamine-type stimulants (ATS) are among illicit stimulant drugs that are most often used worldwide. A major challenge is to develop a fast and efficient methodology involving minimal sample preparation to analyze ATS in biological fluids. In this study, a urine pool solution containing amphetamine, methamphetamine, ephedrine, sibutramine, and fenfluramine at concentrations ranging from 0.5 pg/mL to 100 ng/mL was prepared and analyzed by atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) and multiple reaction monitoring (MRM). A urine sample and saliva collected from a volunteer contributor (V1) were also analyzed. The limit of detection of the tested compounds ranged between 0.002 and 0.4 ng/mL in urine samples; the signal-to-noise ratio was 5. These results demonstrated that the ASAP-MS/MS methodology is applicable for the fast detection of ATS in urine samples with great sensitivity and specificity, without the need for cleanup, preconcentration, or chromatographic separation. Thus ASAP-MS/MS could potentially be used in clinical and forensic toxicology applications.

Immunogenicity and sustainability of the immune response in Brazilian HIV-1-infected individuals vaccinated with inactivated triple influenza vaccine.

HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination.

Versatility of tandem mass spectrometry for focused analysis of oxylipids.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring (MRM) scan mode has been the primary MS method applied for the target identification of specific and minor oxylipids in complex matrices, such as eicosanoids and docosanoids, which are potent lipid mediators derived from polyunsaturated fatty acid oxygenation. However, the high specificity of MRM can limit the detection of species with m/z MRM transitions not covered by the method. In addition to MRM, tandem-quadrupole mass analyzers enable other experiments to be conducted, by fragmenting ions via collision-induced dissociation process (CID). This paper presents the potential of tandem mass spectrometry for the focused analysis of oxylipids. We have successfully developed an LC-MS/MS method for the identification of precursor ions of m/z 115, a diagnostic product ion of 5-hydroxy- and 5-epoxy-fatty acids. As a proof of concept, the developed method was used to discover several oxylipids oxidized at C5 derived from arachidonic acid (C20 : 4) oxygenation in a hypothalamus rat extract that were not identified using the target MRM methodology. The proposed focused MS/MS-based approach in a tandem mass analyzer has proven to be a powerful strategy to accelerate the identification of oxylipids with structural similarities and assist the field of lipidomic research.

Effect of postural insoles on static and functional balance in children with cerebral palsy: a randomized controlled study.

BACKGROUND: Improved gait efficiency is one of the goals of therapy for children with cerebral palsy (CP). Postural insoles can allow more efficient gait by improving biomechanical alignment. OBJECTIVE: The aim of the present study was to determine the effect of the combination of postural insoles and ankle-foot orthoses on static and functional balance in children with CP. METHOD: A randomized, controlled, double-blind, clinical trial. After meeting legal requirements and the eligibility criteria, 20 children between four and 12 years of age were randomly allocated either to the control group (CG) (n=10) or the experimental group (EG) (n=10). The CG used placebo insoles and the EG used postural insoles. The Berg Balance Scale, Timed Up-and-Go Test, Six-Minute Walk Test, and Gross Motor Function Measure-88 were used to assess balance as well as the determination of oscillations from the center of pressure in the anteroposterior and mediolateral directions with eyes open and closed. Three evaluations were carried out: 1) immediately following placement of the insoles; 2) after three months of insole use; and 3) one month after suspending insole use. RESULTS: The EG achieved significantly better results in comparison to the CG on the Timed Up-and-Go Test as well as body sway in the anteroposterior and mediolateral directions. CONCLUSION: Postural insoles led to an improvement in static balance among children with cerebral palsy, as demonstrated by the reduction in body sway in the anteroposterior and mediolateral directions. Postural insole use also led to a better performance on the Timed Up-and-Go Test.

Effect of postural insoles on static and functional balance in children with cerebral palsy: A randomized controlled study

BACKGROUND: Improved gait efficiency is one of the goals of therapy for children with cerebral palsy (CP). Postural insoles can allow more efficient gait by improving biomechanical alignment. OBJECTIVE: The aim of the present study was to determine the effect of the combination of postural insoles and ankle-foot orthoses on static and functional balance in children with CP. METHOD: A randomized, controlled, double-blind, clinical trial. After meeting legal requirements and the eligibility criteria, 20 children between four and 12 years of age were randomly allocated either to the control group (CG) (n=10) or the experimental group (EG) (n=10). The CG used placebo insoles and the EG used postural insoles. The Berg Balance Scale, Timed Up-and-Go Test, Six-Minute Walk Test, and Gross Motor Function Measure-88 were used to assess balance as well as the determination of oscillations from the center of pressure in the anteroposterior and mediolateral directions with eyes open and closed. Three evaluations were carried out: 1) immediately following placement of the insoles; 2) after three months of insole use; and 3) one month after suspending insole use. RESULTS: The EG achieved significantly better results in comparison to the CG on the Timed Up-and-Go Test as well as body sway in the anteroposterior and mediolateral directions. CONCLUSION: Postural insoles led to an improvement in static balance among children with cerebral palsy, as demonstrated by the reduction in body sway in the anteroposterior and mediolateral directions. Postural insole use also led to a better performance on the Timed Up-and-Go Test. .

Enhanced xyloglucan-specific endo-ß-1,4-glucanase efficiency in an engineered CBM44-XegA chimera.

Xyloglucan-specific endo-ß-1,4-glucanases (Xegs, EC 3.2.1.151) exhibit high catalytic specificity for ß-1,4 linkages of xyloglucan, a branched hemicellulosic polysaccharide abundant in dicot primary cell walls and present in many monocot species. In nature, GH12 Xegs are not associated with carbohydrate-binding modules (CBMs), and here, we have investigated the effect of the fusion of the xyloglucan-specific CBM44 on the structure and function of a GH12 Xeg from Aspergillus niveus (XegA). This fusion presented enhanced catalytic properties and conferred superior thermal stability on the XegA. An increased k cat (chimera, 177.03 s(-1); XegA, 144.31 s(-1)) and reduced KM (chimera, 1.30 mg mL(-1); XegA, 1.50 mg mL(-1)) resulted in a 1.3-fold increase in catalytic efficiency of the chimera over the parental XegA. Although both parental and chimeric enzymes presented catalytic optima at pH 5.5 and 60 °C, the thermostabilitiy of the chimera at 60 °C was greater than the parental XegA. Moreover, the crystallographic structure of XegA together with small-angle X-ray scattering (SAXS) and molecular dynamics simulations revealed that the spatial arrangement of the domains in the chimeric enzyme resulted in the formation of an extended binding cleft that may explain the improved kinetic properties of the CBM44-XegA chimera.

Dereplication of Streptomyces sp. AMC 23 polyether ionophore antibiotics by accurate-mass electrospray tandem mass spectrometry.

Actinomycetes, especially those belonging to the genus Streptomyces, are economically important from a biotechnological standpoint: they produce antibiotics, anticancer compounds and a variety of bioactive substances that are potentially applicable in the agrochemical and pharmaceutical industries. This paper combined accurate-mass electrospray tandem mass spectrometry in the full scan and product ion scan modes with compounds library data to identify the major compounds in the crude extract produced by Streptomyces sp. AMC 23; it also investigated how sodiated nonactin ([M + Na](+)) fragmented. Most product ions resulted from elimination of 184 mass units due to consecutive McLafferty-type rearrangements. The data allowed identification of four macrotetrolides homologous to nonactin (monactin, isodinactin, isotrinactin/trinactin and tetranactin) as well as three related linear dimer compounds (nonactyl nonactoate, nonactyl homononactoate and homononactyl homononactoate). The major product ions of the sodiated molecules of these compounds also originated from elimination of 184 and 198 mass units. UPLC-MS/MS in the neutral loss scan mode helped to identify these compounds on the basis of the elimination of 184 and 198 mass units. This method aided monitoring of the relative production of these compounds for 32 days and revealed that the biosynthetic process began with increased production of linear dimers as compared with macrotetrolides. These data could facilitate dereplication and identification of these compounds in other microbial crude extracts.

In vitro metabolism of monensin A: microbial and human liver microsomes models.

1. Monensin A, an important antibiotic ionophore that is primarily employed to treat coccidiosis, selectively complexes and transports sodium cations across lipid membranes and displays a variety of biological properties. 2. In this study, we evaluated the fungi Cunninghamella echinulata var. elegans ATCC 8688A, Cunninghamella elegans NRRL 1393 ATCC 10028B and human hepatic microsomes as CYP-P450 models to investigate the in vitro metabolism of monensin A and compare the products with the metabolites produced in vivo. 3. Mass spectrometry analysis of the products from these model systems revealed the formation of three metabolites: 3-O-demethyl monensin A, 12-hydroxy monensin A and 12-hydroxy-3-O-demethyl monensin A. We identified these products by tandem mass spectrometry and through comparison with the in vivo metabolites. 4. This analysis demonstrated that the model systems produce the same metabolites found in in vivo studies, thus they could be used to predict the metabolism of monensin A. Furthermore, we verified that liquid chromatography coupled to mass spectrometry is a powerful tool to study the in vitro metabolism of drugs, because it allows the successful identifications of several derivatives from different metabolic models.

Assessment of social support and its association to depression, self-perceived health and chronic diseases in elderly individuals residing in an area of poverty and social vulnerability in rio de janeiro city, Brazil.

OBJECTIVES: Social support (SS) influences the elderly ability to cope with the losses of ageing process. This study was aimed at assessing SS among elderly users of a primary healthcare unit in a poor and violent area of Rio de Janeiro City, and at verifying its association with depression, self-perceived health (SPH), marital status and chronic illnesses. METHODS: A cross-sectional study was performed based on a convenience sample of 180 individuals aged 60 years or older. SS was measured with part of the Brazilian version of Medical Outcomes Study's SS scale, and SPH and depression were assessed, respectively, through one question and the Brazilian version of the Structured Clinical Interview for DSM-IV Axis I Disorders. SS medians were calculated for the categories of SPH, depression, marital status and chronic illnesses variables, and differences were evaluated with the Kruskal-Wallis and Mann-Whitney tests. Additionally, Pearson's chi-square test and logistic regression were employed to identify unadjusted and adjusted associations between SS and those variables. RESULTS: The participant's mean age was 73 years old, and level of education was 3 years of school education on average. They were predominantly females (73.3%), and non-married (55.0%). Among them, 74.4% perceived their SS as satisfactory, 55.0% perceived their health as good, 27.8% were diagnosed with major depression and 83.3% had hypertension. Especially for those depressed and with bad SPH, the medians of SS measure were much lower than for others, reaching an unsatisfactory level. Moreover, controlling for other factors, non-depressed individuals were more likely (OR = 2.32) to have satisfactory SS. CONCLUSION: in the violent and poor area explored in this research low SS is highly prevalent in the elderly. Depressed individuals are more likely to have low SS and this condition should be investigated in depressed elderly. The reduced scale is useful for low education individuals.

Biomimetic oxidation studies of monensin A catalyzed by metalloporphyrins: identification of hydroxyl derivative product by electrospray tandem mass spectrometry

Monensin A is an important commercially available natural product isolated from Streptomyces cinnamonensins that shows antibiotic and anti-parasitic activities. This molecule has a significant influence in the antibiotic market, but until now there are no studies on putative metabolite formations. Bioorganic catalysts applying metalloporphyrins and mono-oxygen donors are able to mimic the cytochrome P450 reactions. This model has been employed for natural product metabolism studies affording several new putative metabolites and in vivo experiments confirming the relevance of this procedure. In this work we evaluated the potential of 10,15,20-tetrakis (pentafluorophenyl) porphyrin metal(III) chloride [Fe(TFPP)Cl] catalyst models to afford a putative monensin A metabolite. Oxidation agents such as meta-chloroperoxy benzoic acid, iodosylbenzene, hydrogen peroxide 30 wt.% and tert-butyl hydroperoxide 70 wt.%, were used to investigate different reaction conditions, in addition to the analysis of the influence of the solvent. The quantification of total monensin A conversion and the structure of the new hydroxylated putative metabolite were proposed based on electrospray ionization tandem mass spectrometry analysis. The porphyrin tested, afforded moderate conversions of monensin A in all reaction conditions and the selectivity was found to be dependent on the oxidation/medium employed.

Bioassay-guided isolation of a low molecular weight PHB from Burkholderia sp. with phytotoxic activity.

This work reports on the bioassay-guided isolation and identification of the macrocyclic pentolide 1, a cyclic polyhydroxybutyrate (PHB) with low molecular weight. This metabolite is produced by Burkholderia sp. and it exhibited phytotoxic activity in a Lemna minor bioassay. Its structure was determined by (1)H and (13)C NMR, heteronuclear multiple quantum correlation, heteronuclear multiple bond correlation, IR, and electrospray ionization tandem mass spectrometry analyses. The period for maximum production of the pentolide was optimized and determined on the basis of multiple reaction monitoring experiments at 15 days. The potential of Burkholderia sp. as a producer of higher biopolymers of PHB was also investigated. The methodology employed here accelerated the isolation and characterization of a phytotoxic metabolite whose structure can serve as a model for the synthesis of new classes of herbicides.

H1N1pdm09 adjuvanted vaccination in HIV-infected adults: a randomized trial of two single versus two double doses.

BACKGROUND: Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. METHODOLOGY/PRINCIPAL FINDINGS: Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. CONCLUSIONS/SIGNIFICANCE: Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained. TRIAL REGISTRATION: ClinicalTrials.gov NCT01155037.

[Guidelines of the Brazilian Medical Association for the treatment of social anxiety disorder]. / Diretrizes da Associação Médica Brasileira para o tratamento do transtorno de ansiedade social.

INTRODUCTION: Social anxiety disorder (SAD) is the most common anxiety disorder, usually with no remission, and is commonly associated with significant functional and psychosocial impairment. The Brazilian Medical Association (BMA), with the project named Diretrizes (Guidelines, in English), seeks to develop consensus for the diagnosis and treatment of common diseases. The aim of this article is to present the most important findings of the guidelines on the treatment of SAD, serving as a reference for the general practitioner and specialist. METHOD: The method used was proposed by the BMA. The search was conducted in the databases of MEDLINE (PubMed), Scopus, Web of Science and LILACS, between 1980 and 2010. The strategy used was based on structured questions as PICO (acronym formed by the initials of "patient or population", "intervention, display or exhibition", "control or comparison" and "outcome"). RESULTS: Studies show that the first-line pharmacological treatment for adults and children are serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, whereas cognitive-behavioral therapy is considered the best psychotherapeutic treatment. Moreover, some psychiatric comorbidities were associated with a worse outcome of SAD. CONCLUSIONS: Despite its high prevalence, SAD does not receive adequate attention and treatment. The best choice for the treatment of adults is a combination of cognitive-behavioral psychotherapy with serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. Other options as benzodiazepines or monoamine oxidase inhibitors must be used as second and third choices, respectively.

Follow-up study of unknowingly pregnant women vaccinated against rubella in Brazil, 2001-2002.

BACKGROUND: Brazil conducted mass immunization of women of childbearing age in 2001 and 2002. Surveillance was initiated for vaccination of women during pregnancy to monitor the effects of rubella vaccination on fetal outcomes. METHODS: Women vaccinated while pregnant or prior to conception were reported to the surveillance system. Susceptibility to rubella infection was determined by anti-rubella immunoglobulin (Ig) M and IgG immunoassays. Susceptible women were observed through delivery. Live-born infants were tested for anti-rubella IgM antibody; IgM-seropositive newborns were tested for viral shedding and observed for 12 months for signs of congenital rubella syndrome. Incidence of congenital rubella infection was calculated using data from 7 states. RESULTS: A total of 22 708 cases of rubella vaccination during pregnancy or prior to conception were reported nationwide, 20,536 (90%) of which were from 7 of 27 states in Brazil. Of these, 2332 women were susceptible to rubella infection at vaccination. Sixty-seven (4.1%) of 1647 newborns had rubella IgM antibody (incidence rate, 4.1 congenital infections per 100 susceptible women vaccinated during pregnancy [95% confidence interval, 3.2-5.1]). None of the infants infected with rubella vaccine virus was born with congenital rubella syndrome. CONCLUSIONS: As rubella elimination goals are adopted worldwide, evidence of rubella vaccine safety aids in planning and implementation of mass adult immunization.