Barriers to Optimal Acute Management of Stroke: Perspective of a Stroke Center in Mexico City.

Background: Stroke is a leading cause of death and disability worldwide, particularly in low- and middle-income countries. We aimed to identify the main barriers to optimal acute management of stroke in a referral center. Methods: Demographic data was collected from patients assessed with acute stroke in the emergency department of the Instituto Nacional de Neurología y Neurocirugía (INNN) from January to June 2019. Additionally, a telephone interview was conducted with patients/primary caregiver to know which they considered the main reason for the delay in arrival at INNN since the onset of stroke. Results: 116 patients were assessed [age 65 ± 15 years, 67 (57.8%) men]. Patients consulted other facilities prior to arrival at INNN in 59 (50.9%) cases (range of hospitals visited 1-4), 83 (71.6%) arrived in a private car, with prenotification in only 4 (3.4%) of the total sample. The mean onset-to-door time was 17 h (45 min-10 days). Telephone interviews were done in 61 patients/primary caregivers, stating that they consider the multiple evaluations in other facilities [n = 26/61 (42.6%)] as the main reason for delay in arrival at the ED, followed by ignorance of stroke symptoms and treatment urgency [n = 21/61 (34.4%)]. Conclusion: In this small, retrospective, single center study, the main prehospital barrier to optimal acute management of stroke in a developing country is multiple medical evaluations prior to the patient's transport to a specialized stroke hospital, who mostly arrived in a private car and without prenotification. These barriers can be overcome by strengthening public education and improving patient transfer networks and telemedicine.

IL-10 and socs3 Are Predictive Biomarkers of Dengue Hemorrhagic Fever.

BACKGROUND: Cytokines play important roles in the physiopathology of dengue infection; therefore, the suppressors of cytokine signaling (socs) that control the type and timing of cytokine functions could be involved in the origin of immune alterations in dengue. OBJECTIVE: To explore the association of cytokine and socs levels with disease severity in dengue patients. METHODS: Blood samples of 48 patients with confirmed dengue infection were analyzed. Amounts of interleukins IL-2, IL-4, IL-6, and IL-10, interferon- (IFN-) γ, and tumor necrosis factor- (TNF-) α were quantified by flow cytometry, and the relative expression of socs1 and socs3 mRNA was quantified by real-time RT-PCR. RESULTS: Increased levels of IL-10 and socs3 and lower expression of socs1 were found in patients with dengue hemorrhagic fever (DHF) with respect to those with dengue fever (DF) (p < 0.05). Negative correlations were found between socs1 and both IL-10 and socs3 (p < 0.01). The cutoff values of socs3 (>199.8-fold), socs1 (<1.94-fold), and IL-10 (>134 pg/ml) have the highest sensitivity and specificity to discriminate between DF and DHF. CONCLUSION: Simultaneous changes in IL-10 and socs1/socs3 could be used as prognostic biomarkers of dengue severity.

Mycorrhizal responses in wheat: shading decreases growth but does not lower the contribution of the fungal phosphate uptake pathway.

Effects have been investigated of reduced C supply (induced by shade) on arbuscular mycorrhizal (AM) colonisation, mycorrhizal growth responses (MGRs) and on AM-mediated and direct uptake of phosphate (Pi) (using (32)P) in wheat, a plant that does not usually respond positively to AM colonisation. Shading markedly reduced growth and shoot/root dry weight ratios of both AM and non-mycorrhizal wheat, indicating decreased photosynthetic C supply. However, shading had very little effect on percent root length colonised by Rhizophagus irregularis or Gigaspora margarita or on MGRs, which remained slightly positive or zero, regardless of shade; there were no growth depressions under shade. By 6 weeks, when the contributions of the AM pathway were measured with (32)P supplied in small hyphal compartments, R. irregularis had supplied 23 to 28% of shoot P with no significant effect of shading. Data show that reduced C availability did not reduce the contribution of the AM pathway to plant P, so the fungi were not acting physiologically as parasites. These results support our previous hypothesis that lack of positive MGR is not necessarily the outcome of excessive C use by the fungi or failure to deliver P via the AM pathway.

Evidence of transmission and risk factors for influenza A virus in household dogs and their owners.

BACKGROUND: The possible transmission of influenza A virus between dogs and humans is important, as in Mexico City there are approximately 1·2 million dogs. We present the first evidence of influenza A virus infection in household dogs in Mexico. OBJECTIVES: The objective of this study was to identify the presence of antibodies against influenza A virus in dogs and their owners, as well as the presence of RNA of influenza A virus in nasal exudates of dogs and, thereby, assess the possible transmission of the virus between humans and dogs. METHODS: Serum samples from household dogs and their owners were analyzed to detect the presence of antibodies against three subtypes of human influenza virus (H1N1pdm09, H1N1, and H3N2), as well as subtype H3N8 of equine influenza. We analyzed dog nasal exudates to detect influenza viral RNA. The relationship between the seropositivity of dogs and various factors (age, sex, constantly at home, and seropositivity of owners) was statistically analyzed. RESULTS: Seroprevalence for human influenza in dogs was 0·9% (1 of 113), and it was 4% (5 of 113) for equine influenza. In humans, seroprevalence was 22% for subtype H1N1pdm09, 20% for subtype H1N1, and 11% for subtype H3N2. No significant association (P>0·05) was found between seropositivity and any of the assessed factors. Furthermore, no viral RNA was detected in the nasal exudate samples. CONCLUSIONS: Results revealed seroprevalence of the influenza virus in household dogs in Mexico City. It can be assumed that dogs are currently becoming infected with different subtypes of influenza viruses.

Plasma cytokine levels and cytokine gene polymorphisms in Mexican patients during the influenza pandemic A(H1N1)pdm09.

BACKGROUND: In Mexico, the initial severe cases of the 2009 influenza pandemic virus A (H1N1) [A(H1N1)pdm09] were detected in early March. The immune mechanisms associated with the severe pneumonia caused by infection with this new virus have not been completely elucidated. Polymorphisms in interleukin genes have previously been associated with susceptibility to infectious diseases due to their influence on cytokine production. OBJECTIVES: The present case-control study was performed to compare several immunologic and genetic parameters of patients and controls during the initial phase of the pandemic. STUDY DESIGN: Sixty-five patients who were hospitalized due to infection with the influenza A(H1N1)pdm09 virus and 46 healthy controls were studied. A hemagglutination inhibition assay (HIA) was performed to measure anti-influenza antibody titers in these subjects. Protein levels of the cytokines interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), interferon gamma (IFNγ), transforming growth factor beta (TGFß)1 and TGFß2 were quantified in plasma. Single nucleotide polymorphisms in IL6, IL10 and TNFα were also assessed. RESULTS: Influenza patients had lower antibody titers and produced significantly higher levels of IL-6, IL-10 and TNFα than healthy controls. The frequencies of the TNFα -308G, IL-10 -592C and IL-10 -1082A alleles and the IL10 -1082(A/A) genotype were associated with susceptibility to severe disease, while the haplotypes TNFα AG and IL-10 GTA and GCA were associated with protection from severe disease [P=0.016, OR (CI)=0.11 (0.01-0.96); P=0.0187, OR (CI)=0.34 (0.13-0.85); P=0.013, OR (CI)=0.39 (0.18-0.83)]. CONCLUSIONS: This study demonstrates that the influenza A(H1N1)pdm09 patients and healthy controls have different profiles of immune parameters and that there is an association between IL-10 and TNFα polymorphisms and the outcome of this disease.

Retrospective serological survey of influenza viruses in backyard pigs from Mexico City.

BACKGROUND: In the present study, we analyzed the presence of antibodies to four different influenza viruses (pH1N1, hH1N1, swH1N1, and swH3N2) in the sera of 2094 backyard pigs from Mexico City. The sera were obtained between 2000 and 2009. OBJECTIVES: The aim of this study was to perform a retrospective analysis of the 2000-2009 period to determine the seroprevalence of antibodies against pH1N1, hH1N1, swH1N1, and swH3N2 viruses in sera obtained from backyard pigs in Mexico City. METHODS: Antibody detection was conducted with hemagglutination inhibition assay (HI) using four influenza viruses. We used linear regression to analyze the tendency of antibody serum titers throughout the aforementioned span. RESULTS: We observed that the antibody titers for the pH1N1, swH1N1, and swH3N2 viruses tended to diminish over the study period, whereas the antibodies to hH1N1 remained at low prevalence for the duration of the years analyzed in this study. A non-significant correlation (P > 0.05) between antibody titers for pH1N1 and swH1N1 viruses was observed (0.04). It contrasts with the significance of the correlation (0.43) observed between the swH1N1 and swH3N2 viruses (P < 0.01). CONCLUSIONS: Our findings showed no cross-antigenicity in the antibody response against the same subtype. Antibodies against pH1N1 virus were observed throughout the 10-year study span, implying that annual strains shared some common features with the pH1N1 virus since 2000, which would then be capable of supporting the ongoing presence of these antibodies.

Inflammatory profiles in severe pneumonia associated with the pandemic influenza A/H1N1 virus isolated in Mexico City.

The immune mechanisms underlying the pathogenesis of severe pneumonia associated with the A/H1N1 virus are not well known. The objective of this study was to determine whether severe A/H1N1-associated pneumonia can be explained by the emergence of particular T-cell subsets and the cytokines/chemokines they produced, as well as distinct responses to infection. T-cell subset distribution and cytokine/chemokine levels in peripheral blood and bronchoalveolar lavage (BAL) were determined in patients with severe A/H1N1 infection, asymptomatic household contacts, and healthy controls. Cytokine and chemokine production was also evaluated after in vitro infection with seasonal H1N1 and pandemic A/H1N1 strains. We found an increase in the frequency of peripheral Th2 and Tc2 cells in A/H1N1 patients. A trend toward increased Tc1 cells was observed in household contacts. Elevated serum levels of IL-6, CXCL8, and CCL2 were found in patients and a similar cytokine/chemokine profile was observed in BAL, in which CCL5 was also increased. Infection assays revealed that both strains induce the production of several cytokines/chemokines at 24 and 72 h, however, IL-6, CCL3, and CXCL8 were strongly up-regulated in 72-h cultures in presence of the A/H1N1 virus. Several inflammatory mediators are up-regulated in peripheral and lung samples from A/H1N1-infected patients who developed severe pneumonia. In addition, the A/H1N1 strain induces higher levels of pro-inflammatory cytokines and chemokines than the seasonal H1N1 strain. These findings suggest that it is possible to identify biomarkers of severe pneumonia and also suggest the therapeutic use of immunomodulatory drugs in patients with severe pneumonia associated with A/H1N1 infection.

Molecular characterization of Histoplasma capsulatum isolated from an outbreak in treasure hunters Histoplasma capsulatum in treasure hunters.

BACKGROUND: In Mexico, primary pulmonary histoplasmosis is the most relevant clinical form of the disease. The geographical distribution of specific strains of Histoplasma capsulatum circulating in Mexico has not been fully established. Outbreaks must be reported in order to have current, updated information on this disease, identifying new endemic areas, manner of exposure to the fungi, and molecular characterization of the causative agents. We report a recent outbreak of histoplasmosis in treasure hunters and the molecular characterization of two isolates obtained from these patients. METHODS: Six patients admitted to the National Institute of Respiratory Diseases (INER) in Mexico City presented severe respiratory symptoms suggestive of histoplasmosis. They acquired the infection in the Veracruz (VZ) endemic zone. Diagnosis was made by X-ray and Computed tomography (CT), liver function, immunological techniques, and culture. Identification of H. capsulatum isolates was confirmed by using Polymerase chain reaction (PCR) was conducted with a probe from the M antigen, and the isolates were characterized by means of Random amplification of polymorphic DNA (RAPD)-PCR employed the 1253 oligonucleotide and a mixture of oligonucleotides 1281 and 1283. These were compared to eight reference strain isolates from neighboring areas. RESULTS: X-ray and CT revealed disseminated micronodular images throughout lung parenchyma, as well as bilateral retrocaval, prevascular, subcarinal, and hilar adenopathies, hepatosplenomegaly, and altered liver function tests. Five of the six patients developed disseminated histoplasmosis. Two H. capsulatum strains were isolated. The same band profile was detected in both strains, indicating that both isolates corresponded to the sole H. capsulatum strain. Molecular characterization of the isolates was similar in 100% with the EH-53 Hidalgo human (HG) strain (reference strain integrated into the LAm A clade described for Latin America). CONCLUSIONS: The two isolates appeared to possess the same polymorphic pattern; they are indistinguishable from each other and from EH-53. It is important to remain updated on recent outbreaks of histoplasmosis, the manner of exposure to the fungi, as well as the molecular characterization of the isolates. The severity of cases indicates that this strain is highly virulent and that it is probably prevalent in Hidalgo and Veracruz states.

The fate and efficacy of benomyl applied to field soils to suppress activity of arbuscular mycorrhizal fungi.

A systematic application of the fungicide benomyl was used to follow up the suppression of arbuscular mycorrhizal (AM) colonization and to determine its fungitoxic activity and persistence at different depths. Repeated applications of benomyl reduced AM colonization mainly in the upper 0-4 cm layer of the treated soils. Furthermore, AM colonization decreased with soil depth. The activity and persistence of this fungicide was reduced over small changes in depth in the first 10 cm of the soil profile beneath a semiarid herbland at Brookfield Conservation Park (South Australia). Repeated applications of the fungicide only slightly increased the levels of toxicity in the soils, probably because of biodegradation of the fungicide in soils with a recent history of exposure to the fungicide. The decline in fungicide activity at depth was correlated with a decline in the suppressive effect of the fungicide on the activity of AM fungi.

Actinomycetoma in arm disseminated to lung with grains of Nocardia brasiliensis with peripheral filaments.

Actinomycetomas represent 97.8% of mycetomas in Mexico, where 86.6% are produced by Nocardia brasiliensis. We report a case of actinomycetoma in the arm by Nocardia brasiliensis disseminated to lung. Uncommon grains were observed which present outside peripheral filaments and also numerous filaments loosing the grains. These characteristics of the grains are due probably because for the long treatment with antibiotics of the patient. In situ antibiotic action against the microcolonies is discussed.

Different arbuscular mycorrhizal fungi induce differences in cellular responses and fungal activity in a mycorrhiza-defective mutant of tomato (rmc).

The reduced mycorrhizal colonisation (rmc) mutant of tomato forms different phenotypes with different arbuscular mycorrhizal (AM) fungi. Our aim was to characterise microscopically the cellular responses in plant and fungus in order to reveal how these varied when colonisation was blocked at different stages. Synchronised colonisation coupled with vital staining, autofluorescence and laser scanning confocal microscopy (LSCM) were used to determine how long the AM fungi stay alive during the interactions with rmc, whether nuclear repositioning occurred in the same way as in wild-type interactions and whether there was evidence for deployment of defence responses. The results showed that (1) all the AM fungi tested were attracted to roots of rmc, on which they developed active external mycelium and appressoria, the latter sometimes in higher numbers than on the wild type; (2) plant cellular responses, such as nuclear movement, occurred only when the AM fungus was able to penetrate the epidermal cells of rmc; and (3) plant defence responses such as autofluorescence were observed only transiently and callose deposition was not involved in blocking AM fungi in rmc. The results demonstrate that multi-step AM colonisation is not only an outcome of cellular processes influenced by both plant and fungus, but is also modified by the capacity of different AM fungi to respond to the plant phenotype induced by the rmc mutation.

Adenoviruses C in non-hospitalized Mexican children older than five years of age with acute respiratory infection.

Adenoviruses (AdV) are commonly involved in acute respiratory infections (ARI), which cause high morbidity and mortality in children. AdV are grouped in six species (A-F), which are associated with a wide range of diseases. The aim of this study was to identify the AdV species infecting non-hospitalized Mexican children with ARI symptoms, attending to the same school. For that, a PCR/RFLP assay was designed for a region of the hexon gene, which was chosen, based on the bioinformatical analysis of AdV genomes obtained from GenBank. A total of 100 children's nasopharyngeal samples were collected from January to June, 2005, and used for viral isolation in A549 cells and PCR/RFLP analysis. Only 15 samples produced cytopathic effect, and in all of them AdV C was identified. AdV C was also identified in eight additional nasopharyngeal samples which were negative for viral isolation. In summary, this outpatient population showed a rate of AdV infection of 23%, and only AdV C was detected.

Adenoviruses C in non-hospitalized Mexican children older than five years of age with acute respiratory infection

Adenoviruses (AdV) are commonly involved in acute respiratory infections (ARI), which cause high morbidity and mortality in children. AdV are grouped in six species (A-F), which are associated with a wide range of diseases. The aim of this study was to identify the AdV species infecting non-hospitalized Mexican children with ARI symptoms, attending to the same school. For that, a PCR/RFLP assay was designed for a region of the hexon gene, which was chosen, based on the bioinformatical analysis of AdV genomes obtained from GenBank. A total of 100 children's nasopharyngeal samples were collected from January to June, 2005, and used for viral isolation in A549 cells and PCR/RFLP analysis. Only 15 samples produced cytopathic effect, and in all of them AdV C was identified. AdV C was also identified in eight additional nasopharyngeal samples which were negative for viral isolation. In summary, this outpatient population showed a rate of AdV infection of 23 percent, and only AdV C was detected.

Detection of human papillomavirus and relevant tumor suppressors and oncoproteins in laryngeal tumors.

PURPOSE: The mechanism of larynx oncogenesis is complex and controlled by various factors, most of them involved in cell proliferation and apoptosis. In this study, we evaluated the levels of two suppressor proteins (pRb and p53) and two oncogenic proteins (c-Myc and Bcl-2), as well as the apoptotic levels and the presence of human papillomavirus (HPV) in both tumor types. EXPERIMENTAL DESIGN: Low- or high-risk HPV viral DNA was determined by PCR and in situ PCR; the level of cellular proteins was examined by immunohistochemistry; the presence of apoptotic cells was evaluated by in situ cell death detection. RESULTS: Most laryngeal papillomatosis samples contained low-risk HPV determined by both techniques. However, 25% of laryngeal carcinoma samples were positive for HPV employing PCR or in situ PCR. In papillomatosis, pRb and p53 levels were higher than in normal larynxes, whereas laryngeal cancer presented the lowest levels. c-Myc oncogene expression was very low in normal and cancer tissues but highly increased in papillomatosis. Bcl-2 expression was low and showed no significant difference between laryngeal papillomatosis and normal larynxes. By contrast, Bcl-2 was clearly up-regulated in cancer. Normal larynx samples and those from laryngeal papillomatosis exhibited similar relatively high numbers of apoptotic cells, whereas in malignant tumors, these cells were scarce. CONCLUSION: Our results suggest that HPV is an important risk factor in papillomatosis and in some malignant larynx tumors with a strong participation of cellular genes, specifically involved in proliferation and apoptosis. In benign papillomatosis lesions but not in larynx cancer, high p53 activity might preserve the apoptosis process. In larynx cancer, low p53 levels and high bcl-2 expression may be playing an important role to block apoptosis.

Indoor and outdoor submicrometer particles: exposure and epidemiologic relevance ("the 3 indoor Ls").

Airborne particles represent a very important pollutant with respect to healthy housing conditions. The snag is that in lack of indoor data epidemiological studies focusing on submicron and ultrafine (<100 nm in diameter) particles are usually forced to use outdoor particle concentrations only. On the other hand it is known that people spend most of their time indoors. The aim of this paper is therefore to give a short comprehensive overview of the indoor/outdoor problem with regard to submicron and ultrafine particles, investigating how indoor particle size distributions correlate with outdoor concentrations in the absence of significant indoor sources. In the absence of a major indoor source, total indoor particle number concentrations were always lower than outdoor concentrations. The highest ratios between indoor and outdoor concentrations tend to correlate with lower rather than higher total outdoor particle number concentrations. Concentration ratios depend on particle size. Time lags of the correlation coefficients between the concentrations of indoor and outdoor particles of different diameters have been determined to assess the time the particles need to enter the indoor site through closed modern-type windows. Typical lag times of 0.5-3 h between somewhat smaller indoor particles and somewhat larger outdoor particles have been observed. To assess the resulting particle burden for humans, a suitably weighted average emphasizing indoor aerosol particles must be used. To classify the health effects of particles of different diameters, different decreases of particle number concentrations depending on the particle sizes must be taken into account if indoor concentrations cannot be measured and outdoor concentrations are used in place of indoor measurements. In urban areas, ultrafine particles originate primarily from rapidly increasing traffic, which is the dominating source at many urban sites. The influence of traffic on outdoor and indoor concentrations is therefore of special interest.

Notas sobre epidemiología de infecciones nosocomiales / Notes on epidemiology of nosocomial infections

Breve revisión acerca de las infecciones nosocomiales, de magnitud creciente y trascendencia en lo concerniente a mortalidad. El análisis incluye definición, clasificación, etiología, mecanismos de transmisión y otros factores relativos a agentes causales, ambiente nosocomial, personal que maneja enfermos y el efecto diseminador de ciertos procedimientos y técnicas de trabajo, uso indiscriminado de antibióticos, así como la susceptibilidad particular del huésped y enfermos afectados ya por otros agentes, con sistemas y mecanismos de defensa deteriorados. Prevención y atenuación de las citadas infecciones son expuestos de acuerdo con las recomendaciones y normas de organismos internacionales y que se sintetizan en el establecimiento de programas adecuados de vigilancia epidemiológica acordes con cada hospital, los cuales han de ser orientados, supervisados y valorados por un comité contra infecciones establecido en todo nosocomio