Pathophysiology of chikungunya virus infection associated with fatal outcomes.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.

Conservative management of newborns with 35 weeks or more of gestational age at risk for early-onset sepsis: a Brazilian cohort study

Abstract Objective: To evaluate the conservative management of newborns born at ≥35 weeks of gestational age, at risk for early-onset neonatal sepsis (EOS). Methods: Retrospective, analytic cohort study (2016 to 2019), including newborns ≥35 weeks of gestational at risk of EOS, asymptomatic at birth, managed conservatively in full rooming-in: serial physical examination and clinical observation for at least 48 h. They were classified into three groups, according to the clinical course: asymptomatic (group A), symptomatic for other reasons (group B), and with sepsis (group C). Risk factors, clinical signs and differential diagnoses of sepsis, length of stay, and discharge conditions were evaluated. Results: The authors evaluated 769 asymptomatic newborns at risk of EOS. (mean birth weight 2999 ± 485 g and gestational age 37.6 ± 1.7 weeks, respectively) corresponding to 12.2% of rooming-in admissions. The most prevalent risk factors were colonization by Group B Streptococcus (29%), prolonged rupture membrane duration (21.9%) and preterm labor (21.4%). Most of all of them (53.9%) remained asymptomatic (group A). Group B corresponded for 45.3%, and the most common clinical signs were hypothermia (24.5%), tremors (8.7%) and vomiting (8%). Environmental dysthermia (50.7%), prematurity (20.0%), and feeding intolerance (15.7%) were common in Group B. Laboratory tests were performed in 3.5%. Five patients (one confirmed) comprised group C (0.8/1,000 live births). There were no deaths. The median length of stay was 64 h (IQR 50-93). Conclusion: The rate of clinical/confirmed EOS was low. Most of the symptomatic patients only needed clinical evaluation to rule out sepsis. Management was shown to be safe.

Conservative management of newborns with 35 weeks or more of gestational age at risk for early-onset sepsis: a Brazilian cohort study.

OBJECTIVE: To evaluate the conservative management of newborns born at ≥35 weeks of gestational age, at risk for early-onset neonatal sepsis (EOS). METHODS: Retrospective, analytic cohort study (2016 to 2019), including newborns ≥35 weeks of gestational at risk of EOS, asymptomatic at birth, managed conservatively in full rooming-in: serial physical examination and clinical observation for at least 48 h. They were classified into three groups, according to the clinical course: asymptomatic (group A), symptomatic for other reasons (group B), and with sepsis (group C). Risk factors, clinical signs and differential diagnoses of sepsis, length of stay, and discharge conditions were evaluated. RESULTS: The authors evaluated 769 asymptomatic newborns at risk of EOS. (mean birth weight 2999 ± 485 g and gestational age 37.6 ± 1.7 weeks, respectively) corresponding to 12.2% of rooming-in admissions. The most prevalent risk factors were colonization by Group B Streptococcus (29%), prolonged rupture membrane duration (21.9%) and preterm labor (21.4%). Most of all of them (53.9%) remained asymptomatic (group A). Group B corresponded for 45.3%, and the most common clinical signs were hypothermia (24.5%), tremors (8.7%) and vomiting (8%). Environmental dysthermia (50.7%), prematurity (20.0%), and feeding intolerance (15.7%) were common in Group B. Laboratory tests were performed in 3.5%. Five patients (one confirmed) comprised group C (0.8/1,000 live births). There were no deaths. The median length of stay was 64 h (IQR 50-93). CONCLUSION: The rate of clinical/confirmed EOS was low. Most of the symptomatic patients only needed clinical evaluation to rule out sepsis. Management was shown to be safe.

The role of mound functions and local environment in the diversity of termite mound structures.

Mound structures that soil termites build have diverse morphologies. Previous observational studies documented that mounds are built to provide regulated environments for the termites that live within them and their structures are formed in ways to support this purpose under the influence of the mounds' immediate environment. The objective of this study is to provide a methodology and a predictive computational model to investigate the reason behind the different but systematic shapes of termite mounds, considering all the relevant forces imposed on them and their thermoregulatory and gas-exchange functions. The gas-exchange function accounts for the capacity of the mound to diffuse metabolic gases generated in the mound's underground nest, while the thermoregulatory function satisfies the connection between the underground nest and deep ground temperatures. The proposed predictive model is based on the principles of heat transfer and thermodynamics and allows optimized mechanically stable structures to freely emerge. The results indicate that, while the model is free to generate any mechanically stable structure, under the relevant environmental and metabolic conditions, it produces structures with forms and geometrical characteristics similar to those of natural mounds. Investigation of the connection between the local environment and the mound shapes indicated that the Sun and wind play an important role in the mound structural form. Mounds exposed to stronger solar irradiance exhibit cone-shaped structures that are pointed towards the Sun, while shaded mounds are observed to be vertical domes. The local wind is observed to affect the external shape of the mound by preventing them to grow tall while controlling the features of the internal structure. By investigating the similarities between structures in different regions (i.e., India, Namibia, and Brazil), it is revealed that, unlike mounds with a strong need for gas-exchange, mounds with a significant demand for thermoregulation exhibit deeper nests, thicker external walls, and well-defined cone- (as opposed to the dome-) shaped structures. Overall, the form of termite mounds is strongly correlated to both regulatory functions and local environments, and the resulting mound shape arises as a combination of these factors.

Serologic Evidence of Mammarenaviruses among Wild Rodents in Brazil.

We screened blood samples from 560 wild rodents collected in southeastern Brazil for antibodies to a recombinant nucleoprotein (rN) of Junín virus. Six rodents were antibody positive (1.1%), demonstrating evidence of infection with mammarenaviruses in several species of Brazilian rodents.

Analysis of the nucleocapsid gene brings new insights to the classification of Sigmodontinae-borne hantaviruses.

Hantaviruses, members of the family Bunyaviridae, are the causative agents of hantavirus cardiopulmonary syndrome in South America. Hantaviruses are currently classified into species based on the guidelines provided by the International Committee on Taxonomy of Viruses. However, a new taxonomic system was proposed recently to classify Sigmodontinae-borne hantaviruses, which are divided currently into three phylogenetic clades corresponding to Andes, Laguna Negra, and Rio Mamore. Analyzing complete nucleocapsid gene sequences of all Sigmodontinae-borne hantaviruses, we propose the addition of a new clade and a fourth group to the already established Andes clade, allowing a better classification of the Sigmodontinae-borne hantaviruses.

Detection of Herpesvirus, Enterovirus, and Arbovirus infection in patients with suspected central nervous system viral infection in the Western Brazilian Amazon.

Acute infections of the central nervous system (CNS) can be caused by various pathogens. In this study, the presence of herpesviruses (HHV), enteroviruses (EVs), and arboviruses were investigated in CSF samples from 165 patients with suspected CNS viral infection through polymerase chain reaction (PCR) and reverse transcriptase PCR. The genomes of one or more viral agents were detected in 29.7% (49/165) of the CSF samples. EVs were predominant (16/49; 32.6%) followed by Epstein-Barr virus (EBV) (22.4%), Varicella-Zoster virus (VZV) (20.4%), Cytomegalovirus (CMV) (18.4%), herpes simplex virus (HSV-1) (4.1%), (HSV-2) (4.1%), and the arboviruses (14.3%). Four of the arboviruses were of dengue virus (DENV) and three of oropouche virus (OROV). The detection of different viruses in the CNS of patients with meningitis or encephalitis highlight the importance of maintaining an active laboratory monitoring diagnostics with rapid methodology of high sensitivity in areas of viral hyperendemicity that may assist in clinical decisions and in the choice of antiviral therapy.

Seizures induced by pentylenetetrazole in the adult zebrafish: a detailed behavioral characterization.

Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZ-induced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research.

Dipterans associated with a decomposing animal carcass in a rainforest fragment in Brazil: notes on the early arrival and colonization by necrophagous species.

This study aimed to provide the first checklist of forensically-important dipteran species in a rainforest environment in Northeastern Brazil, a region exposed to high rates of homicides. Using a decomposing pig, Sus scrofa L. (Artiodactyla: Suidae), carcass as a model, adult flies were collected immediately after death and in the early stages of carcass decomposition. To confirm actual colonization of the carcass, insects that completed their larval development on the resource were also collected and reared until adult stage. A diverse assemblage of dipterans composed of at least 28 species from seven families with necrophagous habits was observed within minutes after death. Besides Calliphoridae and Sarcophagidae, species from forensically-important families such as Phoridae, Anthomyiidae, and Fanniidae were also registered. Eleven species were shown to complete their development on the carcass. The majority of individuals emerged from larvae collected at the dry stage of decomposition. Hemilucilia segmentaria Fabricius (Diptera: Calliphoridae), H. semidiaphana (Rondani), and Ophyra chalcogaster (Wiedemann) (Muscidae) were the dominant species among the colonizers, which supports their importance as forensic evidence in Brazil.

Intervenção coronária percutânea em idosos: impacto da faixa etária mais avançado (-> 80 anos) no perfil clínico e nos resultados imediatos / Percutaneos coronary intervention in the elderly: impact of advanced age (->80 years) on the clinical profile and immediate result

Introdução: Com o aumento da longevidade observado nas últimas décadas, as intervenções coronárias percutâneas (ICPs) em octogenários são cada vez mais indicadas, podendo, no entanto, não apresentar os mesmos resultados de pacientes idosos com idade menos avançada. Este estudo comparou os perfis e os resultados imediatos em pacientes idosos com idade > 80 anos e < 80 anos, procurando respostas para esses questionamentos. Método: Estudo de coorte, retrospectivo, que envolveu todos os 998 pacientes idosos tratados no triênio 2008-2010, no Instituto Dante Pazzanese de Cardiologia, divididos em dois grupos: grupo A, 192 (19,2) octogenários; e grupo B, 806 (81,8) pacientes idosos com idades entre 70 anos e 79 anos. Foram incluídos pacientes apresentando quadros clínico e angiográfico com indicação para ICP, de acordo com as diretrizes vigentes. Resultados: Os pacientes do grupo A apresentaram predomínio significante de insuficiência renal crônica (78,6 vs. 54,8; P < 0,01) e tenderam a apresentar mais síndromes coronárias agudas (33,3 vs. 26,6; P = 0,07). As lesões-alvo tipo B2/C também predominaram no grupo A (54,8 vs. 41,2; P < 0,01), porém, a despeito disso, esses pacientes receberam menos stents farmacológicos (18,1 vs. 31,2; P < 0,01). Não foi observada diferença na mortalidade (0 vs. 0,2; P = 0,83) ou na ocorrência de infarto relacionado ao procedimento (5,7 vs. 3,3; P = 0,18). Não houve necessidade da realização de cirurgia de revascularização de urgência em nenhum paciente. Conclusões: Os octogenários, que atualmente correspondem a cerca de 20 dos pacientes tratados por ICP, apresentaram maior complexidade clínica e angiográfica, receberam menos stents com liberação de medicamentos e apresentaram resultados hospitalares semelhantes aos dos menos idosos.

With the increase in longevity observed in the last decades, percutaneous coronary interventions (PCI) in octogenarians are increasingly recommended. However, they may not achieve the same results observed for younger elderly individuals. This study compared the profiles and immediate results of elderly patients > 80 and < 80 years of age. METHODS: We performed a retrospective cohort study including 998 elderly patients treated from 2008 to 2010 at the Instituto Dante Pazzanese de Cardiologia, divided into two groups: group A, 192 (19.2%) octogenarians; and group B, 806 (81.8%) individuals with ages ranging from 70 to 79 years. Patients with clinical and angiographic indications for PCI were included according to the current guidelines. RESULTS: Group A patients had a significant prevalence of chronic renal failure (78.6% vs. 54.8%; P < 0.01) and had a trend towards acute coronary syndrome (33.3% vs. 26.6%; P = 0.07). Type B2/C target lesions were also more frequent in group A (54.8% vs. 41.2%; P < 0.01), however, despite of these findings, these patients received less drug-eluting stents (18.1% vs. 31.2%; P < 0.01). There was no difference in mortality (0 vs 0.2%; P = 0.88) or in the rate of procedure-related myocardial infarction (5.7% vs. 3.3%; P = 0.18). Emergency CABG was not required in any of the patients. CONCLUSIONS: Octogenarians, who currently account for about 20% of the patients treated by PCI, had higher clinical and angiographic complexity, received less drug-eluting stents and had similar in-hospital results to the younger elderly individuals.

Oral lesions associated with HIV infection before and during the antiretroviral therapy era in Ribeirão Preto, Brazil.

We estimated the prevalence of oral lesions associated with human immunodeficiency virus (HIV-OLs) before and during the antiretroviral therapy (ART) era. The first period was 1997, when many patients received two types of antiretroviral (ARV) drugs. The second study period was 2004 through 2008, when all patients were treated with ART (a combination of two or three classes of drugs, including protease inhibitors). A total of 148 and 388 seropositive participants were examined in 1997 and 2004-2008, respectively. The evaluation consisted of anamnesis and physical examination. The prevalence of HIV-OLs decreased between 1997 (60.1%) and 2004-2008 (29.9%). The HIV-OL responsible for the greatest reduction in prevalence between the two periods was oral candidiasis, of which erythematous candidiasis was the clinical form that decreased most, followed by pseudomembranous candidiasis. In conclusion, we observed a significant reduction in HIV-OLs, which was closely associated with the use of ART. In addition, among patients with a clinical diagnosis of AIDS, we confirmed a significant reduction in HIV-OL prevalence between 1997 and 2004-2008.

Uso antenatal do corticosteroide e hemorragia peri-intraventricular: [revisão] / Antenatal corticosteroids and intraventricular hemorrhage: [review]

OBJETIVO: Realizar uma revisão bibliográfica sobre o uso antenatal do corticosteroide na prevenção da hemorragia peri-intraventricular. FONTES DE DADOS: Levantamento bibliográfico por meio do Pubmed e SciELO abrangendo os últimos 20 anos. Foram utilizadas as palavras chaves no idioma inglês: "cerebral hemorrhage", "steroids" e "newborn, infant". SÍNTESES DE DADOS: A hemorragia peri-intraventricular é uma importante patologia nos prematuros, sobretudo nos menores de 34 semanas, devido a suas graves sequelas neurológicas. Uma vez ocorrido o sangramento, não há tratamento específico. Desta forma, a prevenção torna-se o maior objetivo das pesquisas. O resultado da meta-análise de estudos randomizados demonstrou que o corticosteroide antenatal reduz a mortalidade e a incidência da doença de membrana hialina e da hemorragia peri-intraventricular. O efeito protetor na redução do risco da hemorragia peri-intraventricular não está completamente esclarecido. Além de acelerar a maturidade pulmonar, o corticosteroide antenatal estimula a maturação da microvasculatura da matriz germinativa, promove o espessamento da membrana basal, acelera a formação proteica nas junções firmes e estabiliza o fluxo sanguíneo cerebral. Também melhora as condições de nascimento dos fetos pré-termo. CONCLUSÕES: O uso antenatal do corticosteroide associado à implementação de melhores práticas de atendimento ao prematuro tem sido responsável pela evidente redução dos índices dessa doença. Apesar de comprovada eficácia e segurança, não é amplamente utilizado. Medidas devem ser tomadas para estimular seu uso como prática rotineira no atendimento de gestantes com risco de parto prematuro.

OBJECTIVE: To conduct a literature review on the use of antenatal corticosteroids for the prevention of peri-intraventricular hemorrhage. DATA SOURCE: Bibliography search in Pubmed and SciELO databases covering the past 20 years using the following key-words: "cerebral hemorrhage", "steroids" and "newborn infant". DATA SYNTHESIS: The peri-intraventricular hemorrhage is an important disease of preterm infants, especially those with less than 34 weeks, due to its serious neurological sequelae. Once the bleeding occurs, there is no specific treatment. Thus, prevention becomes the main goal of the research. Meta-analysis of randomized studies showed that antenatal corticosteroids reduce mortality and the incidence of hyaline membrane disease and peri-intraventricular hemorrhage. The physiologic basis for this protective effect in reducing the risk of peri-intraventricular hemorrhage is not completely clear. Besides accelerating lung maturity, antenatal steroids stimulate the maturation of the microvasculature of the germinal matrix, promote the thickening of the basement membrane, accelerate the formation of protein in tight functions and stabilize the cerebral blood flow. They also improve the birth conditions of preterm babies. CONCLUSIONS: The use of antenatal corticosteroids associated with implementing best practices to assist preterm infants reduces the frequency of peri-intraventricular hemorrhage. Despite its proven efficacy and safety, it is not widely used. Measures should be taken to encourage its use as a routine practice in the care of pregnant women at risk of premature birth.

Algorithms to predict cerebral malaria in murine models using the SHIRPA protocol.

BACKGROUND: Plasmodium berghei ANKA infection in C57Bl/6 mice induces cerebral malaria (CM), which reproduces, to a large extent, the pathological features of human CM. However, experimental CM incidence is variable (50-100%) and the period of incidence may present a range as wide as 6-12 days post-infection. The poor predictability of which and when infected mice will develop CM can make it difficult to determine the causal relationship of early pathological changes and outcome. With the purpose of contributing to solving these problems, algorithms for CM prediction were built. METHODS: Seventy-eight P. berghei-infected mice were daily evaluated using the primary SHIRPA protocol. Mice were classified as CM+ or CM- according to development of neurological signs on days 6-12 post-infection. Logistic regression was used to build predictive models for CM based on the results of SHIRPA tests and parasitaemia. RESULTS: The overall CM incidence was 54% occurring on days 6-10. Some algorithms had a very good performance in predicting CM, with the area under the receiver operator characteristic ((au)ROC) curve > or = 80% and positive predictive values (PV+) > or = 95, and correctly predicted time of death due to CM between 24 and 72 hours before development of the neurological syndrome ((au)ROC = 77-93%; PV+ = 100% using high cut off values). Inclusion of parasitaemia data slightly improved algorithm performance. CONCLUSION: These algorithms work with data from a simple, inexpensive, reproducible and fast protocol. Most importantly, they can predict CM development very early, estimate time of death, and might be a valuable tool for research using CM murine models.

Torcicolo congênito: avaliação de dois tratamentos fisioterapêuticos / Congenital torticollis: evaluation of two physiotherapeutic approaches

OBJETIVO: Avaliar a evolução clínica e comparar a eficácia do tratamento fisioterapêutico intensivo ou mínimo, em neonatos e lactentes com torcicolo congênito. MÉTODOS: Foram atendidas no Ambulatório de Fisioterapia e Cirurgia Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas 47 crianças com torcicolo congênito. Analisaram-se, retrospectivamente, antecedentes maternos, neonatais, apresentação clínica e tratamento fisioterapêutico, classificado de acordo com a freqüência das sessões. O tratamento intensivo foi definido como sessões de fisioterapia realizadas pelo fisioterapeuta no ambulatório, acrescidas de exercícios diários realizados pelos pais em domicílio. O tratamento mínimo foi considerado quando apenas o fisioterapeuta realizava as sessões semanalmente no ambulatório, sem a participação dos pais. RESULTADOS: Quanto às características demográficas da população, observou-se: idade média materna=26 anos; parto normal=40 (85 por cento); mães primigestas=35 (75 por cento); idade média ao diagnóstico=50 dias. A presença de nódulo intramuscular foi notada em 46 (98 por cento) pacientes. As seguintes doenças estiveram associadas: luxação congênita de quadril igual=4 (8 por cento); fratura de clavícula=2 (4 por cento); pé torto congênito=1 (2 por cento). O tratamento intensivo foi realizado em 34 (72 por cento) pacientes e a cura observada em 100 por cento, após 74 dias, em média. O tratamento mínimo foi aplicado em 13 (28 por cento) pacientes e a cura observada em dez (77 por cento), tratados em média por 130 dias. CONCLUSÕES: O torcicolo congênito apresentou evolução clínica favorável em ambos os grupos. O tratamento intensivo propiciou maior índice de cura em menor tempo de tratamento.

OBJECTIVE: To evaluate the clinical course and to compare the effectiveness of physiotherapeutic treatment performed daily or once a week in newborns and infants with congenital torticollis. METHODS: 47 patients with congenital torticollis were assisted at the Physiotherapy and Pediatric Surgery Services of the Clinical Hospital of Campinas University. The following data were retrospectively collected: maternal and neonatal history, clinical presentation and physiotherapeutic treatment classified according to the frequency of the exercises. Intensive treatment was defined as sessions performed at the daycare clinic by the physiotherapist plus daily sessions performed by parents at home. Minimal treatment was defined as weekly sessions performed only by the physiotherapist at the daycare clinic, without participation of the parents. RESULTS: The demographic characteristics of the studied patients were: mean maternal age=26 years; first gestation=35 (75 percent); vaginal delivery=40 (85 percent); mean age at diagnosis =50 days. A sternomastoid nodule was felt seen in 46 (98 percent) patients. Diseases associated with congenital torticollis were: congenital hip dislocation=4 (8 percent); fracture of clavicles=2 (4 percent); and club feet=1 (2 percent). Intensive treatment was performed in 34 (72 percent) patients for an average of 74 days and the cure was achieved in 100 percent. Minimal treatment was performed in 13 (28 percent) for an average of 130 days and ten (77 percent) patients achieved cure. CONCLUSIONS: Congenital torticollis had favorable outcome in both groups. The intensive treatment was followed by higher rates of cure in smaller period of time.

Mechanisms of shock in hantavirus pulmonary syndrome.

PURPOSE OF REVIEW: Despite abundant literature on hantavirus, few reports have focused on the shock in hantavirus pulmonary syndrome. This review approaches recent advances that allow us to better understand the pathogenesis of hantavirus pulmonary syndrome shock. RECENT FINDINGS: Hantavirus pulmonary syndrome has been studied in a hamster model that mimics human shock and respiratory failure. In-vitro experiments show that pathogenic hantaviruses are able to inhibit antiviral responses, and that cytotoxicity of hantavirus-specific T cells enhances the permeability of infected endothelial cells. The idea that the primary cardiac lesion of shock is mostly functional has been shaken by the report of a typical myocarditis in hearts from human hantavirus pulmonary syndrome fatal cases. The involvement of regulatory T cells on hantavirus persistence in its rodent reservoir suggests that these cells could protect from severe hantavirus pulmonary syndrome and shock. SUMMARY: Hantavirus pulmonary syndrome shock is probably related to an exacerbated immune response of CD8+ T cells producing cytotoxicity on infected endothelial cells, presence of myocarditis and myocardial depression induced by nitric oxide. The virulence elements in G1 glycoprotein could also contribute to shock. Active suppression of immune T regulatory cells is probably involved in hantavirus pulmonary syndrome pathogenesis. These are all new aspects of hantavirus pulmonary syndrome pathogenesis that stimulate further studies to elucidate mechanisms of shock and to develop effective treatment strategies.

Hantavirus infection induces a typical myocarditis that may be responsible for myocardial depression and shock in hantavirus pulmonary syndrome.

Despite clinical evidence of myocardial dysfunction, there is no pathological evidence of myocardial injury in hantavirus pulmonary syndrome (HPS). The dominant opinion is that the primary cardiac lesion is functional rather than structural. The present study describes hantaviral antigen and particles in the cardiac endothelium and interstitial macrophages in association with a typical myocarditis in HPS. Human hearts from 14 individuals who died of HPS were compared with hearts from 14 individuals who died of acute necrotizing pancreatitis associated with acute lung injury and 4 individuals who died accidental deaths without thoracic injury (as controls); all cases were selected from autopsies. Transmural blocks of myocardial tissue were excised from the middle portion of the left-ventricular free wall and fixed in formalin. Small samples of myocardial tissue from 4 HPS cases and 4 non-HPS controls were fixed in glutaraldehyde for electron microscopic study. Histomorphometric, immunohistochemical, and ultrastructural methods were employed to detect the presence of hantavirus in the myocardium and to evaluate interstitial edema and the minor diameter of myocytes, to characterize the immunophenotype, and to estimate the number of inflammatory cells and in situ cytokine-producing cells and the T helper cell subset 1 and 2 immune responses (tumor necrosis factor [TNF]-alpha, interferon-gamma, interleukin [IL]-10, and IL-4). Cardiac remodeling; hantaviral antigen and particles in the endothelium and macrophages; scattered foci of myofiber necrosis; greater interstitial cellular infiltration, mainly composed of macrophages and memory T lymphocytes and a significant number of T helper and B lymphocytes; and TNF-alpha protein expression in macrophage-type cells and cardiomyocytes were observed to a greater extent in HPS myocardium than in normal and acute pancreatitis control myocardium. These findings give support to the opinion that structural changes could be responsible for myocardial depression and shock in HPS, and it should be properly named as "hantavirus cardiopulmonary syndrome" (HCPS).

[Dengue: sero-epidemiological survey and virological surveillance in Campinas, São Paulo, Brazil]. / Dengue: inquérito populacional para pesquisa de anticorpos e vigilância virológica no Município de Campinas, São Paulo, Brasil.

The epidemiology of dengue in the municipality of Campinas, São Paulo, Brazil, was studied in 1998 using a randomized sero-epidemiological survey. Epidemiological surveillance data from 1996-2003 were also analyzed, with an emphasis on virological surveillance. 1,260 individuals participated in the survey and had blood samples drawn by finger stick on filter paper. Blood samples were tested by EIA-ICC, an enzyme immunoassay using infected cells as antigen. Dengue antibody prevalence (14.79%) was lower than in other surveys in other States of Brazil, but higher than in two other serological surveys in São Paulo State. Dengue antibody prevalence was far higher than the reported case incidence during the 1996, 1997, and 1998 epidemics. Antibody prevalence and reported case incidence in different health districts were disproportional. The article concludes by recommending further research on the significance of transmission rates during epidemics and more intensive virological surveillance, especially in years with few reported cases.

Alterações bucais em crianças prematuras e com baixo peso ao nascer / Buccal problems in premature and low birth weight children

Objetivo: revisar as alterações bucais decorrentes da prematuridade e do baixo peso ao nascimento e as medidas preventivas primárias e secundárias. Fontes de dados: pesquisa nas bases de dados Medline e Lilacs, bem como sites na internet, livros técnicos e publicações nacionais e internacionais, abrangendo o período de 1976 até 2006. Os termos utilizados foram "nascimento prematuro" e "baixo peso ao nascimento". Síntese dos dados: as alterações decorrentes da prematuridade e do baixo peso ao nascimento se manifestam na má formação do esmalte dentário e do palato, assim como no atraso do crescimento e desenvolvimento das dentições decídua e permanente. Estas alterações podem afetar a estética e predispor os dentes à cárie dentária, além de favorecer a presença de maloclusão. Desta forma, veriofica-se a necessidade e a importância dos cuidados educativos e preventivos a essas crianças o mais precocemente possível, evitando problemas futuros. Conclusões: os cuidados preventivos voltados à criança prematura são imprescindíveis para a manutenção de sua saúde bucal, possibilitando o crescimento e o desenvolvimento adequado do sistema estomatognático, sendo evidende a necessidade de atuação multiprofissional.

Dengue: inquérito populacional para pesquisa de anticorpos e vigilância virológica no Município de Campinas, São Paulo, Brasil / Dengue: sero-epidemiological survey and virological surveillance in Campinas, Sao Paulo, Brazil

Estudou-se a epidemiologia do dengue no Município de Campinas, São Paulo, Brasil, por meio de um inquérito populacional aleatório realizado em 1998, visando à detecção dos níveis de anticorpos para dengue, e de dados de vigilância epidemiológica do período de 1996 a 2003, com ênfase na vigilância virológica. Foram coletadas 1.260 amostras, por meio de punção digital, utilizando-se papel de filtro, sendo as amostras testadas pelo teste imunoenzimático em culturas celulares infectadas (EIA-ICC). Observou-se que a prevalência de soro reagentes (14,79 por cento) é mais baixa que as encontradas em outros inquéritos realizados no país e superior às encontradas em dois inquéritos realizados em cidades do Estado de São Paulo. Detectou-se uma prevalência de soro reagentes muito superior à incidência de casos notificados e confirmados laboratorialmente durante as epidemias de 1996, 1997 e 1998. Não se encontrou proporcionalidade entre a prevalência de anticorpos para dengue e a incidência de casos durante a epidemia nos diferentes Distritos de Saúde da cidade. Sugerem-se um estudo aprofundado do significado dos indicadores de transmissão utilizados em epidemias e uma vigilância virológica mais intensa, principalmente em anos com níveis de transmissão baixos.

The epidemiology of dengue in the municipality of Campinas, São Paulo, Brazil, was studied in 1998 using a randomized sero-epidemiological survey. Epidemiological surveillance data from 1996-2003 were also analyzed, with an emphasis on virological surveillance. 1,260 individuals participated in the survey and had blood samples drawn by finger stick on filter paper. Blood samples were tested by EIA-ICC, an enzyme immunoassay using infected cells as antigen. Dengue antibody prevalence (14.79 percent) was lower than in other surveys in other States of Brazil, but higher than in two other serological surveys in São Paulo State. Dengue antibody prevalence was far higher than the reported case incidence during the 1996, 1997, and 1998 epidemics. Antibody prevalence and reported case incidence in different health districts were disproportional. The article concludes by recommending further research on the significance of transmission rates during epidemics and more intensive virological surveillance, especially in years with few reported cases.