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Introduction. Fungal infections caused by yeast have increased in recent decades, becoming a major threat to public health. Hypothesis/Gap Statement. Antifungal therapy represents a challenging problem because, in addition to presenting many side effects, fungal resistance has been increasing in recent years. As a result, the search for new therapeutic agents has advanced with the use of new technologies such as nanoparticles (NPs). Aim. Synthesize, characterize and evaluate the antifungal potential of naringenin (NAR)-stabilized silver NPs. Methodology. The biosynthesis of NPs was stabilized using the NAR molecule and an aqueous solution of silver nitrate. The characterization of silver nanoparticles (AgNPs) was performed using different methods, which include UV-visible spectroscopy, powder X-ray diffraction (XRD), transmission electron microscopy, zeta potential measurements and Fourier transform infrared (FTIR) spectroscopy. Antifungal activity was evaluated against clinical isolates of Candida albicans by determining the MIC and the minimum fungicidal concentration (MFC). Results. The AgNP NAR showed a colloidal appearance with an average size of 14.71 nm and zeta potential measured at -33.3 mV, indicating a highly stable suspension. XRD analysis confirmed the crystal structure. FTIR spectra showed the presence of several functional groups of plant compounds, which play an important role in the coating and bioreduction processes. The antifungal activity against C. albicans showed an MIC of 3.55 µg ml -1 and an MFC of 7.1 µg ml -1 . According to the growth kinetic assay in 12 h, there was a reduction of ~50% (<3 log10). Furthermore, AgNP NAR did not show mutagenic potential. Conclusion. The AgNP NAR obtained presented ideal characteristics for biomedical applications, good stability and promising antimicrobial activity.

Introduction: Treatments for Parkinson's disease (PD) focus on symptom reduction through dopaminergic therapies, without clear evidence of disease-modifying effects. Glucagon-like peptide-1 (GLP-1) receptor agonists may reduce neuroinflammation by decreasing microglia activation in PD. Clinical trials suggest these agents have disease-modifying potential in PD., Objective: Evaluate the efficacy of GLP-1 receptor agonists in PD., Methods: PubMed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs) of GLP-1 agonists for PD, up to July 2024. The risk of bias was assessed using the RoB-2 tool, and statistical analysis was performed with RevMan 5.4.1 software., Results: GLP-1 receptor agonists showed a beneficial effect on MDS-UPDRS part III motor scores compared to placebo. Off-medication state, there was a -1.22 point improvement (95%CI -2.46, 0.22; P = 0.05). On-medication state, scores improved by -2.52 points (95%CI -4.02, -1.01; P = 0.001). The global MDS-UPDRS score showed a -3.43-point difference (95%CI -6.48, -0.48; P = 0.02). Cognitive performance, assessed via the Mattis DRS-2, improved by 1.32 points (95%CI 0.16, 2.52; P = 0.03). There were no significant differences in the NMSS (-0,19; 95%IC -3,44, 3,05; P = 0.91), in MADRS (-1,04; 95%IC -2,57, 0,48; P = 0.18), or PDQ-39 (-0,91; 95%IC -2,22, 0,39; P = 0.17)., Conclusion: GLP-1 receptor agonists improved motor and cognitive performance in PD, suggesting potential symptomatic benefits. However, further studies are needed to evaluate their long-term effects and their role in disease modification, especially considering ethnic and disease severity variations., 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 © 2024 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the anti -Mycobacterium tuberculosis ( Mtb ) potential of the hybrid oxadiazol-4-methoxynaphthalene ( 6n ) derived from N -acylhydrazone ( 4k ). Materials & methods: The study determined the minimal inhibitory concentration of ( 6n) against Mtb H 37 Rv and Mtb clinical isolates, potential combination of ( 6n) with anti-tuberculosis drugs and carried out time kill curve assay of Mtb H 37 Rv. Additional contribution for the analysis of (6n) was explored by in silico pharmacokinetics, and in vitro and in vivo cytotoxicity determinations. Results: The newly synthesized molecule ( 6n) demonstrated anti- Mtb activity, low cytotoxicity and selectivity for Mtb. Conclusion: The derivative ( 6n ) emerges as a potential anti-TB drug candidate.

Objective: HPV infection is considered the most common sexually transmitted virus today. The persistence of HPV is the main cause for the development of precursor lesions and cervical cancer. There are environmental and non-environmental factors that contribute to the persistence of the virus. Studies indicate a possible relationship between the vaginal microbiota (environmental factor) and the risk of high-grade cervical squamous intraepithelial lesions and cervical cancer. This study evaluates the association between the type of vaginal microbiota and the occurrence of high-grade squamous intraepithelial lesions of the cervix., Methods: Observational, longitudinal, prospective, and analytical studies carried out between 2019 and 2021, which evaluated the vaginal microbiota of patients diagnosed with high-grade cervical squamous intraepithelial lesion before and after treatment in two collections with an interval of 6 months, using scrapings and vaginal swabs., Results: In Group I (with lesions) 28 women participated and 29 in Group II (without lesions). According to Nugent, in the initial collection of Group I, 16 women (57%) had lactobacillary microbiota, eight (28%) intermediate, and four (14%) coccus. In Group II, twenty-one (75%) were lactobacillary, one (3%) was intermediate, and seven (24%) werecoccus. With p=0.03., Conclusion: According to Nugent's criteria, there was an association between the type of vaginal microbiota and the occurrence of high-grade cervical squamous intraepithelial lesions of the cervix. The same was not observed in the Donders classification. Studies with a larger sample are needed to confirm our results., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Objective: This study investigated the combination of Bauhinia holophylla (Bong.) Steud. leaf extracts with conventional antifungal agents, highlighting the extracts' potential as adjuvants in treating oral candidiasis., Design: Ethanolic and aqueous extracts of B. holophylla leaves were analyzed using ultra-high-performance liquid chromatography with a diode array detector (UHPLC-DAD) to assess their chemical composition. Their Minimum Inhibitory Concentration (MIC) against standard strains of Candida albicans and isolates from oral mucosa was determined. Additionally, the potential synergistic effects with chlorhexidine gluconate, nystatin, and fluconazole were investigated, along with their impact on inhibiting and disrupting biofilm formation, germ tube formation of C. albicans, and cytotoxicity in human erythrocytes., Results: Protocatechuic acid, epicatechin, and rutin were identified in both extracts. They exhibited fungistatic activity with a median minimum inhibitory concentration (MIC 50 ) of 15.62 µg/mL for the ethanolic extract (EEB) and 62.50 µg/mL for the aqueous extract (AEB) against C. albicans. In growth kinetics, both extracts reduced the viable cell count of C. albicans by 2 logs after 24 h compared to the positive control. The extracts reduced germ tube formation by 81.6 % for EEB and 86.3 % for AEB. The synergistic combination with fluconazole and nystatin resulted in a 50 % reduction in the concentration required to inhibit C. albicans growth. No hemolytic activity was detected in human erythrocytes at the tested concentrations., Conclusion: Both ethanolic and aqueous extracts show promising potential as adjuvants in managing oral candidiasis. Notably, the aqueous extract is advantageous due to its non-toxic solvent, cost-effectiveness, and ease of preparation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefani de Oliveira Rosa reports financial support was provided by Coordination of Higher Education Personnel Improvement. Kelly Mari Pires de Oliveira reports financial support was provided by Foundation for Support and Development of Education Science and Technology of Mato Grosso do Sul State. Kelly Mari Pires de Oliveira reports financial support was provided by National Council for Scientific and Technological Development. If there are other authors, they 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 © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To use three-dimensional anorectal ultrasonography (3D-US) to evaluate the outcome of ligation of the intersphincteric fistula tract (LIFT) in patients with crypto-glandular transsphincteric fistula and describing the patterns of healing, failure, and recurrence rate., Methods: After classifying the fistula and determining the length of the sphincter muscle to be transected, the patients were submitted to LIFT. The accuracy of pre- and postoperative 3D-US with 360° endoprobe (16 MHz) with automatic scanning and clinical findings was evaluated against surgical findings. Three outcomes were considered: healing, failure (persistent anal fistula through the original external opening or intersphincteric), and recurrence (reappearance of the anal fistula)., Results: Sixty-three patients of both sexes were evaluated. The 3D-US assessment revealed primary healing in 50 (79.3%) patients, although in 6 (9.5%) cases healing was delayed and the cavity was without communication with the anal canal. The procedure failed in 9 (15.9%) and fistula recurred in 4 (6.3%), all of whom underwent a second surgery based on a new 3D-US, resulting in a 92.3% (12/13) healing rate on 3D-US., Conclusions: A 3D-US was found to be useful in the preoperative assessment of fistulas by quantifying the percentage of muscle to be transected, and in the postoperative assessment by identifying healing, types of failure, and recurrence. The 3D-US was accurate and consistent with surgical findings., (© 2024 American Institute of Ultrasound in Medicine.)

Background: Few studies measured the pre- and postoperative anatomic and functional anal canal using 3-dimensional endoanal ultrasound and anal manometry and correlated sphincter division with fecal incontinence, severity, and function., Objective: To assess the incidence of fecal incontinence in patients who underwent internal anal sphincter division for anal fissure or intersphincteric anal fistula and correlate severity of symptoms with percentage of divided muscle, anatomical measurements, and anal pressures., Design: Prospective cohort study., Settings: Colorectal surgery unit, tertiary referral center., Patients: Patients underwent clinical assessment using the Cleveland Clinic Florida Fecal Incontinence score for severity of symptoms, manometry, and ultrasound., Main Outcomes Measures: Ultrasound measurements of length, percentage, and angle of divided internal anal sphincter, anterior external anal sphincter, posterior external anal sphincter plus puborectalis, and gap lengths., Results: Sixty-three women (mean age, 44 years) were divided into 2 groups: 30 (48%) underwent fistulotomy for intersphincteric anal fistula and 33 (52%) underwent sphincterotomy for chronic anal fissure with high anal resting pressure. Forty-six percent experienced some measure of fecal incontinence after internal anal sphincter division. Incidence of fecal incontinence, severity of symptoms, and angle of the divided internal anal sphincter were similar between the groups. Length and percentage of the divided internal anal sphincter were significantly higher in the intersphincteric anal fistula. External anal sphincter and external anal sphincter plus puborectalis lengths were similar in both groups. Gap length was significantly longer in chronic anal fissures with high anal resting pressure., Limitations: Single-institution, exclusion of males., Conclusions: Fecal incontinence was reported in half of the patients who underwent internal anal sphincter division. Despite the greater length and percentage of internal anal sphincter division in patients who underwent fistulotomy, incidence and severity of fecal incontinence were similar in both groups. Three-dimensional endoanal ultrasound showed greater gap length in the sphincterotomy group, which may be functionally significant after the division of the shorter internal anal sphincter but with a similar impact on fecal incontinence in both groups., Impacto De La Divisin Del Esfnter Anal Interno En La Alteracin De La Continencia En Pacientes De Sexo Femenino: ANTECEDENTES:Pocos estudios han medido el canal anal anatómico y funcional antes y después de la cirugía mediante ecografía endoanal tridimensional y manometría anal, y correlacionado la división del esfínter con la incontinencia fecal, la gravedad y la función.OBJETIVO:Evaluar la incidencia de incontinencia fecal en pacientes sometidos a división del esfínter anal interno por fisura anal o fístula anal interesfinteriana, y correlacionar la gravedad de los síntomas con el porcentaje de músculo dividido, las medidas anatómicas y las presiones anales.DISEÑO:Estudio de cohorte prospectivo.AJUSTE:Unidad de cirugía colorrectal, centro de referencia de tercer nivel.PACIENTES:Pacientes sometidos a una evaluación clínica utilizando la puntuación de incontinencia fecal de Cleveland Clinic Florida para la gravedad de los síntomas, la manometría y la ecografía.PRINCIPALES MEDIDAS DE RESULTADO:Mediciones por ultrasonido de la longitud, el porcentaje y el ángulo del esfínter anal interno dividido y el esfínter anal externo anterior, el esfínter anal externo posterior más el puborrectal y las longitudes del espacio.RESULTADOS:Sesenta y tres mujeres (edad media, 44 años) se dividieron en 2 grupos: 30 (48%) sometidos a fistulotomía por fístula anal interesfinteriana y 33 (52%) sometidos a esfinterotomía por fisura anal crónica con alta presión anal en reposo. El 46% experimentó algún grado de incontinencia fecal después de la división del esfínter anal interno. La incidencia de incontinencia fecal, la gravedad de los síntomas y el ángulo del esfínter anal interno dividido fueron similares entre los grupos. La longitud y el porcentaje del esfínter anal interno dividido fueron significativamente mayores en la fístula anal interesfinteriana. Las longitudes del esfínter anal externo y del esfínter anal externo más el puborrectal fueron similares en ambos grupos. La longitud del espacio fue significativamente mayor en la fisura anal crónica con alta presión anal en reposo.LIMITACIONES:Institución única, exclusión de varones.CONCLUSIÓN:La incontinencia fecal se reportó en la mitad de los pacientes sometidos a división del esfínter anal interno. A pesar de la mayor longitud y porcentaje de división del esfínter anal interno en los pacientes sometidos a fistulotomía, la incidencia y gravedad de la incontinencia fecal fue similar en ambos grupos. La ecografía endoanal tridimensional mostró una mayor longitud del espacio en el grupo de esfinterotomía, lo que puede ser funcionalmente significativo después de la división del esfínter anal interno más corto, pero con un impacto similar en la incontinencia fecal en ambos grupos. (Traducción-Dr. Fidel Ruiz Healy )., (Copyright © The ASCRS 2023.)

In the current study, two euglossine species, Exaerete smaragdina and Eulaema nigrita, a cleptoparasite bee and its host, respectively, were used as models to: (i) access the genetic diversity and population structure of both species, sampled along a wide latitudinal range of Atlantic Forest, where the distribution of El. nigrita and Ex. smaragdina co-occurs; (ii) investigate the evolutionary history of these species through the Atlantic Forest, and in a wider scenario, to examine the evolutionary history of these species across others forest domains. Analyses involved males of El. nigrita and Ex. smaragdina sampled through Brazilian territory, including 19 sites in the Atlantic Forest. Bayesian Skyline Plot (BSP) was used to infer possible climate oscillations on population of both species over time. The BSP revealed stability in effective population size for both species in most of the Plio-Pleistocene period. However, BSP results aligned to the starlike configuration in the haplotype network, neutrality test, and population diversity patterns indicated population expansion of the two species during the late Pleistocene. Our findings suggest areas of potential refugia to the climatic oscillations of the Pleistocene in the Atlantic Forest in the Brazilian states of Espírito Santo for El. nigrita and Pernambuco for Ex. smaragdina.

Background: In hospital settings, dermatology can offer substantial clinical support for the diagnosis and management of skin conditions, reducing morbidity and mortality. Thus, the study aimed to analyze the profile of referrals and consultations performed by the Dermatology Service of the Santa Casa de Misericordia de Porto Alegre, from August 2018 to January 2020., Methods: This study is descriptive, quantitative, and retrospective, conducted through data collection and review of medical records and referrals. The variables included were clinical data of referrals, in-patients profiles, dermatological diagnoses, complementary exams, therapeutic conduct, and recommended follow-ups., Results: A total of 1020 referrals were analyzed, which resulted in 641 consultations (328 men, 313 women). The most prevalent skin disease groups were 'Dermatitis and Eczema' (33.1%) and 'Other infectious skin diseases (21.8%), while the most frequent ICD-10 were 'Drug eruptions - L27' (9.9%) and 'Other and unspecified dermatitis - L30' (6.6%). Corticoids were the most recommended treatments (27.7%), followed by antifungals (13.1%). 'Consultation Discharge' (44%) and 'Outpatient' Dermatology follow-up (27%) were the most frequent causes for ending consultation., Study Limitations: Among the study limitations, the authors highlight its retrospective nature, with data analysis based on referrals and medical records, which may present inaccurate or incomplete information. In addition to this, the study may demonstrate a certain degree of subjectivity due to the review and interpretation process conducted by the researchers. However, the definition of objective criteria based on previous studies attenuates such possible bias. Furthermore, considering that the Dermatology teams are composed of a preceptor dermatologist and residents, the established diagnoses were not submitted to third-party verification, except in the cases of skin biopsies and cultures. Thus, the professional's experience and skills may have influenced the dermatological diagnoses., Conclusions: These findings underlie the importance of Dermatology in hospital assistance, contributing to the management of a wide range of skin conditions., (Copyright © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Human activity directly or indirectly causes climate change, promoting changes in the composition of the atmosphere. This change is beyond the variation of the natural climate. In this manner, climate change could create an environmental pressure which is enough to trigger new fungal diseases. In addition to climate alterations, the onset of the COVID-19 pandemic has also been associated with the emergence of fungal pathogens. Fungi showed that an inability to grow at high temperatures limits the capacity of fungi to infect mammals. However, fungi can develop thermotolerance, gradually adapting to rising temperatures due to climate change, and generating a greater number of disease-causing organisms. In the present study, we reported the detection and identification of Candida palmioleophila isolates recovered from raw sewage samples in Niteroi city, Rio de Janeiro State, Brazil, during a monitoring program for measuring SARS-CoV-2 presence and concentration. Using polyphasic taxonomy to identify the species and evaluating some virulence aspects of this species, such as biofilm formation and extracellular enzyme production, our data highlight this species as a possible emerging pathogen in Brazil, especially in the pandemic context.

Objectives: Identifying and mapping the literature regarding sexual violence against Brazilian boys and men, as well as describing its underreporting, prevalence, and associated factors., Methods: We conducted a scoping review by searching PubMed, Biblioteca Digital Brasileira de Teses e Dissertações, Biblioteca Virtual em Saúde, Scopus, and Web of Science databases. The inclusion criteria were: (a) surveys including data on sexual violence; (b) inclusion of boys or men as victims of sexual violence; (c) presenting statistical data on prevalence, underreporting, and factors associated with sexual violence among Brazilian boys and men., Results: We found a total of 1,481 papers. Ultimately, 53 were included and had their data extracted. Most studies are quantitative in nature (n = 48). The total number of participants across studies was 1,416,480 and the prevalence of sexual violence ranged from 0.1% to 71%. It is important to note that underreporting statistical data was cited in several studies. The group with the highest prevalences was men who have sex with men and those with sexual dysfunctions. Increased tendency to drug use, social isolation, unprotected anal sex, suicidal ideation, sexual dysfunction, and post-traumatic stress disorder were statistically significant predictors for having experienced sexual violence., Conclusions: Despite the prevalence of sexual violence being high against Brazilian boys and men, this area of is surprisingly understudied and there are few studies with this exclusive scope. Social cultural issues, such as sexism, contribute to the underreporting of sexual violence. Additionally, we identified issues related to mental, sexual and reproductive health to be associated with sexual violence. Based on our findings, we recommend the implementation and development of a structural infrastructure aimed at supporting boys and men who are victims of sexual violence, and preventing negative outcomes for this affected group.

Objectives: Ocrelizumab demonstrated significant clinical benefit for the treatment of relapsing (RMS) and primary progressive (PPMS) multiple sclerosis (MS), an incurable disease characterized by disability progression. This study evaluated the clinical and economic impact of ocrelizumab relative to current clinical practice, including other disease-modifying therapies (DMT), available in Portugal., Methods: Markov models for MS were adapted to estimate the impact of ocrelizumab across three patient populations: treatment-naïve RMS, previously treated RMS, and PPMS. Health states were defined according to the Expanded Disability Status Scale. For RMS, the model further captured the occurrence of relapses and progression to secondary progressive multiple sclerosis (SPMS). A lifetime time-horizon and Portuguese societal perspective were adopted., Results: For RMS patients, ocrelizumab was estimated to maximize the expected time (years) without progression to SPMS (10.50) relative to natalizumab (10.10), dimethyl fumarate (8.64), teriflunomide (8.39), fingolimod (8.38), interferon β-1a (8.33) and glatiramer acetate (8.18). As the most effective option, with quality-adjusted life year (QALY) gains between 0.3 and 1.2, ocrelizumab was found to be cost-saving relative to natalizumab and fingolimod, and presented incremental cost-effectiveness ratios (ICER) below €16,720/QALY relative to the remaining DMT. For PPMS patients, the ICER of ocrelizumab versus best supportive care was estimated at €78,858/QALY., Conclusions: Ocrelizumab provides important health benefits for RMS and PPMS patients, comparing favourably with other widely used therapies. In RMS, ocrelizumab was revealed to be either cost-saving or have costs-per-QALY likely below commonly accepted cost-effectiveness thresholds. In PPMS, ocrelizumab fills a clear clinical gap in the current clinical practice. Overall, ocrelizumab is expected to provide good value for money in addressing the need of MS patients., (© 2022. The Author(s).)

Most studies of sexual violence are with women, and although men who have sex with men (MSM) is the group of the men that has been most investigated for sexual violence, there are still several questions to be answered about sexual violence and sexual revictimization among MSM. This study aimed to estimate the prevalence of sexual violence in different stages of life and identify factors associated with sexual violence in adulthood among Brazilian MSM. We conducted an analysis with data from the study conducted in 2016 with 4,176 MSM from 12 Brazilian cities recruited through respondent-driven sampling (RDS), who answered a survey to a set of questions, among which some specific about sexual violence. Most participants were under 25 years old (56.5%), with more than 12 years of schooling (71.2%), mixed race (40.8%), single (86.2%), and belonging to some religion (50.9%). The lifetime prevalence of sexual violence was 20.3%. In our analyses, having experienced sexual violence in childhood and adolescence increased the odds of experiencing sexual violence in adulthood (prevalence ratio ratios [PRR] 4.93 (95% CI [1.99, 12.21]), as did experiencing physical violence (PRR 1.99; 95% CI [1.07, 3.71]) and receiving money for sex (PRR 2.26; 95% CI [1.17, 4.36]). In addition to violence in childhood and adolescence being risk factors for sexual violence in adulthood, we also observed that half of the sample experienced sexual violence repeatedly, characterizing sexual revictimization. It is important that health services are prepared to receive boys and men victims in order to reduce the chances of revictimization and other outcomes.

Entomopathogenic nematodes (EPNs) from Heterorhabditidae and Steinernematidae families are extensively used to control insect pests. In Brazil, however, relatively few studies have identified and characterized these entomopathogens. The objective of this study was to identify and characterize an EPN isolate obtained from soil samples collected in the state of Paraná, Brazil. An isolate (UEL 08) of Heterorhabditis was detected in a soil sample collected from a pasture area cultivated with Brachiaria grass in Londrina, state of Paraná, Brazil (23°34'311''S, 050°58'298''W), using the insect-baiting technique with Galleria mellonella larvae as hosts. The nematode was identified through morphometric studies and molecular analyses based on amplification of the rDNA ITS region. Although we identified certain morphometric differences compared with the original description, the molecular data indicated that the ITS sequence obtained for the UEL 08 isolate is identical to the reference sequence of H. amazonensis (DQ665222) and presented 100% similarity. Thus, the findings of our morphological and molecular studies confirmed that the isolated nematode is H. amazonensis, which is the first time this species has been registered in Paraná. Study of the biological characteristics of H. amazonensis (UEL 08) revealed that the isolate has two distinct life cycles - one short (216 h) and the other long (288 h) - and produces two generations in both cycles. We observed that H. amazonensis (UEL 8) was pathogenic and virulent to the three evaluated hosts, although with different virulence against these hosts. The larvae of G. mellonella and Alphitobius diaperinus were more susceptible than adult Dichelops (Diacereus) melacanthus, with 100%, 85%, and 46% mortality, respectively. Furthermore, an in vivo production assay revealed a mean daily yield of 3.4 × 103 infective juveniles/g host larvae.

We present the case of a 32-year-old man with a diagnosis of type-III osteogenesis imperfecta who developed a telangiectatic osteosarcoma in the proximal right tibia. An above-knee amputation was performed and after one-year follow-up, pulmonary metastatic lesions were detected on the thoracic CT scan. Palliative chemotherapy was proposed and to date the patient is still living and is under medical treatment. The association between osteogenesis imperfecta and osteosarcoma is rare. There are only ten confirmed reports of this unusual situation, but to our knowledge this is the first case reported with a telangiectatic osteosarcoma arising in this particular setting.

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A 2A receptor (A 2A R) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A 2A R in age-related conditions. We report, for the first time, a significant overexpression of A 2A R in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A 2A R overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca 2+ influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A 2A R blockade. This A 2A R/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity.

Purpose: Chronic obstructive pulmonary disease promotes systemic repercussions, which can be minimized with physical exercise. This study investigated the effects of a water-based aerobic interval training program on the autonomic modulation of heart rate (HR), quality of life (QoL), and functional capacity (FC) of patients with chronic obstructive pulmonary disease., Methods: Nineteen patients with chronic obstructive pulmonary disease were enrolled in this randomized clinical trial and allocated to either the usual care group (n = 9) or training group (n = 10). Before and after 24 sessions of water-based physical training, the patients underwent evaluation of autonomic modulation of HR by analyzing the HR variability, QoL using the St George's Respiratory Questionnaire, and FC using 6-min walk test distance., Results: The results showed significant improvement when comparing the variables of HR variability, QoL, and FC in the training group in the pre- and post-training conditions (P < .05). In the usual care group, there was no significant difference for any of the variables. Negative correlations were found between HR variability and QoL (r =-0. 55; P = .01) and 6-min walk test distance and QoL (r =-0.49; P = .02)., Conclusion: Water-based physical training promoted beneficial adaptations in the autonomic modulation of HR, QoL, and FC of patients with chronic obstructive pulmonary disease.

Gymnogeophagus setequedas is a rare and rheophilic species of tribe Geophagini, considered endangered in Brazilian red lists. Its previously known geographical distribution range was the Paraná River basin, in Paraguay, and a tributary of the Itaipu Reservoir in Brazil. Since its description no specimens have been collected in the original known distribution area. However, recent records of G. setequedas in the lower Iguaçu River, in a region considered highly endemic for the ichthyofauna, extended the known geographical distribution and may represent one of the last remnants of the species. The aim of this study was to estimate the genetic diversity and population structure of G. setequedas , using microsatellite markers and mitochondrial haplotypes, in order to test the hypothesis of low genetic diversity in this restricted population. Muscular tissue samples of 86 specimens were obtained from nine locations in the Lower Iguaçu River basin, between upstream of the Iguaçu Falls and downstream of the Salto Caxias Reservoir. Seven microsatellites loci were examined and a total of 120 different alleles were obtained. The number of alleles per locus ( N A ) was 17.429, effective alleles ( N E ) 6.644, expected heterozygosity ( H E ) 0.675, observed ( H O ) heterozygosity 0.592, and inbreeding coefficient ( F IS ) 0.128. Twelve haplotypes in the D-Loop region were revealed, with values of h (0.7642) and π (0.00729), suggesting a large and stable population with a long evolutionary history. Thus, both molecular markers revealed high levels of genetic diversity and indicated the occurrence of a single G. setequedas population distributed along a stretch of approximately 200 km. The pattern of mismatch distribution was multimodal, which is usually ascribed to populations in demographic equilibrium. Nevertheless, the construction of a new hydroelectric power plant, already underway between the Salto Caxias Reservoir and Iguaçu Falls, could fragment this population, causing loss of genetic diversity and population decline, and for this reason it is necessary to maintain the Iguaçu River tributaries and downstream area from the Lower Iguaçu Reservoir free of additional dams, to guarantee the survival of this species.

Synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders that are characterized by the accumulation of α-synuclein (aSyn) in intracellular inclusions known as Lewy bodies. Prefibrillar soluble aSyn oligomers, rather than larger inclusions, are currently considered to be crucial species underlying synaptic dysfunction. We identified the cellular prion protein (PrP C ) as a key mediator in aSyn-induced synaptic impairment. The aSyn-associated impairment of long-term potentiation was blocked in Prnp null mice and rescued following PrP C blockade. We found that extracellular aSyn oligomers formed a complex with PrP C that induced the phosphorylation of Fyn kinase via metabotropic glutamate receptors 5 (mGluR5). aSyn engagement of PrP C and Fyn activated NMDA receptor (NMDAR) and altered calcium homeostasis. Blockade of mGluR5-evoked phosphorylation of NMDAR in aSyn transgenic mice rescued synaptic and cognitive deficits, supporting the hypothesis that a receptor-mediated mechanism, independent of pore formation and membrane leakage, is sufficient to trigger early synaptic damage induced by extracellular aSyn.

Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium ([Ca2+] i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular [Ca2+]i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-κB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-κB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases.

Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Abnormal accumulation of aggregated α-synuclein (aSyn) is a hallmark of sporadic and familial Parkinson's disease (PD) and related synucleinopathies. Recent studies suggest a neuroprotective role of adenosine A2A receptor (A2AR) antagonists in PD. Nevertheless, the precise molecular mechanisms underlying this neuroprotection remain unclear. We assessed the impact of A2AR blockade or genetic deletion (A2AR KO) on synaptic plasticity and neuronal cell death induced by aSyn oligomers. We found that impairment of LTP associated with aSyn exposure was rescued in A2AR KO mice or upon A2AR blockade, through an NMDA receptor-dependent mechanism. The mechanisms underlying these effects were evaluated in SH-SY5Y cells overexpressing aSyn and rat primary neuronal cultures exposed to aSyn. Cell death in both conditions was prevented by selective A2AR antagonists. Interestingly, blockade of these receptors did not interfere with aSyn oligomerization but, instead, reduced the percentage of cells displaying aSyn inclusions. Altogether, our data raise the possibility that the well-documented effects of A2AR antagonists involve the control of the latter stages of aSyn aggregation, thereby preventing the associated neurotoxicity. These findings suggest that A2AR represent an important target for the development of effective drugs for the treatment of PD and related synucleinopathies., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Streams are very important environments for Neotropical freshwater fish fauna, and possess a high number of species. These small drainages are also highlighted by their intrinsic biological and physicochemical features; however, knowledge on the genetic distribution of fish in these drainages is limited. Therefore, in the present study, RAPD (random amplified polymorphic DNA) and microsatellite markers were used to analyze population differentiation and gene flow of Astyanax altiparanae and Geophagus brasiliensis from three sites (high, medium, and low) throughout the Penacho stream (about 32 km long), which is a Neotropical stream. Both markers revealed higher levels of genetic diversity levels for A. altiparanae (: 90.05; H S : 0.350) compared to G. brasiliensis (: 30.43; H S : 0.118), which may be related to the particular biology of each species. AMOVA revealed significant genetic variation among populations of each species. All pairwise Φ ST values were significant, ranging from 0.020 to 0.056 for A. altiparanae samples, and from 0.065 to 0.190 for G. brasiliensis samples. Bayesian clustering analysis corroborated these results and revealed clusters of both A. altiparanae (two based on RAPD data) and G. brasiliensis (two based on RAPD data and three on microsatellite data). Gene flow estimates showed that there were similar rates of migration among A. altiparanae samples and low rates of migration among some G. brasiliensis samples. These results suggest patterns of fine-scale genetic structure for both species in the Penacho stream. This information may enhance knowledge of Neotropical streams and may be useful for future management and conservation activities.

Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A2AR over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A2AR overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by GR in the hippocampus are amplified by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we demonstrate that A2AR act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A2AR is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer's and age-related cognitive impairments may rely on its ability to modulate GR actions.

The article analyzes the quality of information of deaths from external causes in Fortaleza, in the State of Ceará, Brazil. They analyzed the completeness of the information of the death certificate (DO) and the correlation between the underlying cause of death described in the OF and registered in the Mortality Information System (SIM ).We used all the original statements of deaths from external causes, occurred in 2010, of residents in Fortaleza. The study population was 2109 DO. The statements were individually checked seeking to identify the completion of the fields and the basic cause attested the coding of the underlying cause in this DO and compared with the SIM was held. The fields with the highest completion rates were: name (100%), place of residence (100%), mother's name (99.6%), place of birth (99.1%), and sex (98.8%). The fields with the lowest completion rates were: place of occurrence (55%), race/skin color (38.4%), and schooling (34%). They observed inadequacies in the completion of the underlying cause. In DO are reported injuries found and not the circumstances of the death. There was poor level of concordance between the basic cause of DO and registered on the SIM (kappa 0.07). They suggest awareness strategies and training of medical examiners.

Most studies of diversity and genetic structure in neotropical fish have focused on commercial species from large rivers or their reservoirs. However, smaller tributaries have been identified as an important alternative migratory route, with independent pools of genetic diversity. In this context, the present study aimed to evaluate genetic diversity and structure in five neotropical fish species from a region of Laranjinha River in the upper Paraná River basin. PCR-RAPD (random amplified polymorphic DNA) markers were used to characterize around 40 individuals of each species distributed upstream and downstream of Corredeira Dam that interrupts the river. The descriptive index of genetic diversity (P = 30.5-82%; HE 0.122-0.312) showed that the populations have acceptable levels of genetic diversity. The values for Nei's genetic distance (DN min 0.0110 and max 0.0306) as well as the genetic structure index and the analysis of molecular variance (AMOVA, ϕST min 0.0132 and max 0.0385) demonstrated low, but significant levels of genetic structure. Bayesian analysis of assignment found two k clusters, including several individuals with mixed ancestry for all populations from the five species analyzed. These findings along with historical data on rainfall and the low dimensions of the dam studied here support the hypothesis that periodic floods enable the transit of individuals between different localities mitigating the differentiation process between populations.

This study details 13 novel polymorphic microsatellite loci in the armoured catfish Hypostomus ancistroides, and assesses their utility for population genetic studies. The analysis of 30 individuals revealed a total of 99 different alleles (ranging from two to 15 alleles per locus), with an average of 7·62 alleles per locus, with observed and expected heterozygosities ranging from 0·103 to 0·931 and from 0·102 to 0·906, respectively. One of the 13 loci showed significant deviations from Hardy-Weinberg equilibrium, probably due to the presence of null alleles, inferred from the excess of homozygotes., (© 2015 The Fisheries Society of the British Isles.)

Objective: To describe the clinical and laboratory presentation of hemophagocytic lymphohistiocytosis in children treated at a referral institution., Methods: A retrospective descriptive study was carried out of seven children diagnosed with hemophagocytic lymphohistiocytosis between 2010 and 2012. The criteria for diagnosis were those proposed by the Histiocyte Society. When indicated, immunochemotherapy was prescribed according to the HLH94 and HLH2004 protocols of the Histiocyte Society., Results: The patients' ages at diagnosis ranged from one month to nine years. All patients had splenomegaly, fever, anemia, thrombocytopenia, hyperferritinemia and hypertriglyceridemia. Bone marrow hemophagocytosis was detected in six patients. In six cases, infectious diseases triggered the syndrome. In two cases, associated with visceral leishmaniasis, remission was achieved after treatment of the underlying infection. Three patients, who had Epstein-Barr-related hemophagocytic lymphohistiocytosis, required treatment with immunochemotherapy. They are alive and in remission; one patient had symptoms of juvenile rheumatoid arthritis and another, who was suspected of having primary hemophagocytic lymphohistiocytosis, entered into remission after bone marrow transplantation. Two deaths (28.6%) occurred in patients with suspected primary hemophagocytic lymphohistiocytosis; one whose clinical picture was triggered by cytomegalovirus infection did not respond to immunochemotherapy and the other died before any specific treatment was provided., Conclusion: As reported before, hemophagocytic lymphohistiocytosis has a multifaceted presentation with nonspecific signs and symptoms. In secondary forms, remission may be achieved by treating the underlying disease. In the primary forms, remission may be achieved with immunochemotherapy, but bone marrow transplantation is required for cure., (Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Adenosine A2A receptors (A2AR) are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well-established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer's disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine-related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR)] and aged-matched wild-types (WT) of the same strain (Sprague-Dawley) were studied. The forced swimming test (FST), sucrose preference test (SPT), and the open-field test (OFT) were performed to evaluate behavioral despair, anhedonia, locomotion, and anxiety. Tg(CaMKII-hA2AR) animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48 h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR) rats exhibit depressive-like behavior, hyperlocomotion, and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress, and Alzheimer's disease.

Fourteen polymorphic microsatellite loci were isolated and characterized for the Neotropical cichlid Geophagus brasiliensis and tested on 30 individuals belonging to a single population. Among the 14 loci described, four showed potential presence of null alleles, inferred from the excess of homozygous genotypes, and three of these loci showed significant deviations from Hardy-Weinberg equilibrium. Fifty-nine different alleles were detected (ranging from two to eight alleles per locus), with estimates of observed and expected heterozygosity ranging from 0·167 to 0·700 and from 0·269 to 0·825. Cross-amplification of primers was successful in five other cichlid species., (© 2013 The Fisheries Society of the British Isles.)

In situations of hypoxia, glutamate excitotoxicity induces neuronal death. The release of extracellular adenosine is also triggered and is accompanied by an increase of the stress mediator, corticotrophin-releasing factor (CRF). Adenosine A(2A) receptors contribute to glutamate excitoxicity and their blockade is effective in stress-induced neuronal deficits, but the involvement of CRF on this effect was never explored. We now evaluated the interaction between A(2A) and CRF receptors (CRFR) function, upon glutamate insult. Primary rat cortical neuronal cultures (9 days in vitro) expressing both CRF(1)R and CRF(2)R were challenged with glutamate (20-1000 μM, 24 h). CRF(1)R was found to co-localize with neuronal markers and CRF(2)R to be present in both neuronal and glial cells. The effects of the CRF and A(2A) receptors ligands on cell viability were measured using propidium iodide and Syto-13 fluorescence staining. Glutamate decreased cell viability in a concentration-dependent manner. Urocortin (10 pM), an agonist of CRF receptors, increased cell survival in the presence of glutamate. This neuroprotective effect was abolished by blocking either CRF(1)R or CRF(2)R with antalarmin (10 nM) or anti-Sauvagine-30 (10 nM), respectively. The blockade of A(2A) receptors with a selective antagonist SCH 58261 (50 nM) improved cell viability against the glutamate insult. This effect was dependent on CRF(2)R, but not on CRF(1)R activation. Overall, these data show a protective role of CRF in cortical neurons, against glutamate-induced death. The neuroprotection achieved by A(2A) receptors blockade requires CRF(2)R activation. This interaction between the adenosine and CRF receptors can explain the beneficial effects of using A(2A) receptor antagonists against stress-induced noxious effects., (© 2012 International Society for Neurochemistry.)

We discuss methods for optimally inferring the synaptic inputs to an electrotonically compact neuron, given intracellular voltage-clamp or current-clamp recordings from the postsynaptic cell. These methods are based on sequential Monte Carlo techniques ("particle filtering"). We demonstrate, on model data, that these methods can recover the time course of excitatory and inhibitory synaptic inputs accurately on a single trial. Depending on the observation noise level, no averaging over multiple trials may be required. However, excitatory inputs are consistently inferred more accurately than inhibitory inputs at physiological resting potentials, due to the stronger driving force associated with excitatory conductances. Once these synaptic input time courses are recovered, it becomes possible to fit (via tractable convex optimization techniques) models describing the relationship between the sensory stimulus and the observed synaptic input. We develop both parametric and nonparametric expectation-maximization (EM) algorithms that consist of alternating iterations between these synaptic recovery and model estimation steps. We employ a fast, robust convex optimization-based method to effectively initialize the filter; these fast methods may be of independent interest. The proposed methods could be applied to better understand the balance between excitation and inhibition in sensory processing in vivo.

State space methods have proven indispensable in neural data analysis. However, common methods for performing inference in state-space models with non-Gaussian observations rely on certain approximations which are not always accurate. Here we review direct optimization methods that avoid these approximations, but that nonetheless retain the computational efficiency of the approximate methods. We discuss a variety of examples, applying these direct optimization techniques to problems in spike train smoothing, stimulus decoding, parameter estimation, and inference of synaptic properties. Along the way, we point out connections to some related standard statistical methods, including spline smoothing and isotonic regression. Finally, we note that the computational methods reviewed here do not in fact depend on the state-space setting at all; instead, the key property we are exploiting involves the bandedness of certain matrices. We close by discussing some applications of this more general point of view, including Markov chain Monte Carlo methods for neural decoding and efficient estimation of spatially-varying firing rates.

The aim of this study was to verify the use of outpatient health services and associated factors among women ages 20 to 60 years living in the urban area of São Leopoldo, Rio Grande do Sul State, Brazil. This was a cross-sectional, population-based study with a sample of 1,026 women in 2003. The association between the independent variables and the outcome was evaluated by means of prevalence ratios and 95% confidence intervals (95%CI). Poisson regression was used with a hierarchical model. Among 1,022 women, 136 (13.3%; 95%CI: 11.2-15.4) had not used outpatient services in the 12 months prior to the interview. Women in lower socioeconomic classes (C, D, and E), with less schooling, and with lower income showed lower use of outpatient health services. Thus, the most vulnerable women and those with the greatest health needs showed the lowest use of health services, suggesting unfavorable conditions in the local health system and pointing to the presence of lack of universal care and equal access.

Antimicrobial susceptibility was determined for 174 Haemophilus influenzae strains collected from patients with infection before and after vaccination against Hib (1990-1999 and 2000-2003, respectively) from 4 public health -laboratories in 3 Brazilian states. All strains were characterized for serotype and beta-lactamase production and in vitro activity of the following antimicrobial agents: -ampicillin, amoxicillin/clavulanate, ceftriaxone, rifampin, chloramphenicol, and trimethoprim/sulfamethoxazole (TMP-SMX). Minimum inhibitory concentrations were determined according to the guidelines of the National Committee for Clinical Laboratory Standards. Overall, ampicillin resistance was observed in 29 strains (17%), all beta-lactamase producers. All isolates were susceptible to amoxicillin/clavulanate and ceftriaxone. The prevalence of TMP-SMX-resistant isolates increased from 32.6% in the period 1990-1999 to 65.8% during the period 2000-2003. Among these isolates, 10.0% and 12.5% were resistant to ampicillin and chloramphenicol, respectively. Resistance to rifampin was detected in 8.2% and 9.7% of the strains, in 2 periods, respectively. Continued surveillance is necessary to monitor trends with the H. influenzae disease in Brazil.

Few vaccines in history have induced such a dramatic decline in incidence over such a short period of time as the Haemophilus influenzae type b (Hib) conjugate. This vaccine was introduced in 1988 in the United States, but only in 1999 was Hib immunization introduced by the Brazilian Ministry of Health as part of the routine infant National Immunization Program. The authors analyzed 229 H. influenzae (Hi) isolates from Public Health Laboratories in three Brazilian states: Pernambuco (Northeast, N = 54), Santa Catarina (South, N = 19), and Rio de Janeiro (Southeast, N = 156). The isolates were collected from Brazilian children 0-10 years of age with meningitis and other infections from 1990 to 2003 and were part of the research collection of the National Institute of Quality Control in Health, FIOCRUZ. Bacterial strains were characterized by serotyping and biotyping. During the pre-vaccination period the prevalence infection due to Hib was of 165 isolates and only 2 non-b Hi among all the notified meningitis infections caused by Hi. Our results showed a significant decrease in the prevalence of Hib meningitis from 165 to 33 isolates after 1999. However, during the post-vaccination period of 2001-2003 we observed an increase in the number of non-b Hi isolates: only 2 non-b strains isolated from 1990 to 1999 and 29 from 1999 to 2003. Based on the present data, the authors emphasize the need for more sensitive epidemiological and bacteriological studies aiming the improvement of the available Hib vaccine, in order to protect the susceptible population to infections due to other serological types of Hi and the reevaluation of immunization schedules used by the National Immunization Program.