6,037 research outputs found
Nitric oxide metabolites as biomarkers for influenza-like acute respiratory infections presenting to the emergency room
Aims: Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic. Methods: Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR. Results: Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to undetectable (interquartile range [IQR], 0 - 2 μM), while median nitrate was 3.4 μM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children with RSV subtype B-associated ILI had higher nitrate compared to all other viruses combined (P=0.002). Conclusion: Concentration of NO-derived nitrate in nasal secretions in children in the ED is suggestive of viral pathogen causative for ILI, and thus might be of clinical utility. Predictive potential of this putative biomarker for ILI needs further evaluation in sicker patients in a prospective manner
Effect of dietary organic acids and humic substance supplementation on performance, immune response and gut morphology of broiler chickens
This study evaluated the additive effects of a commercial feed supplementation blend (Ava Cid P)—consisting of humic substances, coated sodium butyrate, and a small acidifier portion— on the growth, immune response, and gut health of broiler chickens. A total of 540 female and 540 male broilers were raised from 1–49 d. On the first day, the animals were distributed in a completely randomized 2 × 5 factorial design (2 sexes and 5 treatments) with 7 replications of 15 birds each. The 5 treatments were 1) birds did not receive Ava Cid P (control); 2) birds received 0.91 kg/t of Ava Cid P from 1–21 d (AVA1–21); 3) birds received 0.91 kg/t of Ava Cid P from 1–21 d and 0.45 kg/t from 22–35 d (AVA1–35); 4) birds received 0.91 kg/t of Ava Cid P from 1–21 d and 0.45 kg/t from 22–42 d (AVA1–42); and 5) birds received 0.91 kg/t of Ava Cid P from 1–21 d, 0.45 kg/t from 22–35 d, and 0.23 kg/t from 36–49 d (AVA1–49). ANOVA and Tukey’s tests were applied to compare the means (P < 0.05) between treatments. The Ava Cid P showed no effect on male or female growth performance or goblet cell density. However, the supplement modified gut morphometry, and jejunum villi were 32% higher at 9 and 35 d in the AVA1–35 birds compared with those of the control group. The apparent villus surface and villus height increased by 87% and 46%, respectively, in the AVA1–49 birds compared with the AVA1–21 birds. The expression of mucin 2 (MUC2) and tumor necrosis factor-alpha (TNF-α) were 1.6% and 0.9% lower in the AVA1–21 birds than in the control birds, but no effects were observed for interleukin-1 beta and interleukin-10. The Ava Cid P altered the mRNA expression of MUC2 and TNF-α and some characteristics of intestinal morphometry, but did not change the performance of broilers
Anisotropy in the dielectric spectrum of hydration water and its relation to water dynamics
Proteins, molecules, and macromolecular assemblies in water are surrounded by
a nanometer-sized hydration layer with properties very different from bulk
water. Here, we use classical molecular dynamics simulations to study the
dielectric response of hydration water next to hydrophobic and hydrophilic
planar surfaces. We find the interfacial dielectricabsorption of water to be
strongly anisotropic: compared to bulk water, which shows a broad
dielectricabsorption maximum around 15 GHz in the imaginary part of the
dielectric function, the absorption for electric fields parallel to the
surface is of similar strength and shows a slight redshift, while for
perpendicular electric fields it is strongly attenuated and blueshifted. This
anisotropy is generic for hydrophobic and hydrophilic surfaces. From our
spatially resolved dielectric functions and a modified Maxwell-Garnett theory
that accounts for anisotropic hydration layers around spherical particles, the
dielectricabsorption of solutions of organic molecules and micelles is derived
to exhibit the experimentally known attenuation in combination with a
redshift. These two features are traced back to the subtle interplay of
interfacial depolarization effects and the dielectricanisotropy in the
hydration layer. By a detailed analysis of the individual water molecule
dynamics the perpendicular blueshift is shown not to be linked to accelerated
water reorientation, but rather to dielectric boundary effects. Carefully
conducted angularly resolved experiments at planar aqueous interfaces will be
able to resolve this dielectricanisotropy and thus to confirm the subtle
connection between spectralabsorption features and the molecular water
dynamics in hydration layers
Clinical manifestations and epidemiology of adolescent tuberculosis in Ukraine
BACKGROUND: During adolescence, childhood and adult forms of tuberculosis (TB) overlap, resulting in diverse disease manifestations. Knowing which patient characteristics are associated with which manifestations may facilitate diagnosis and enhance understanding of TB pathophysiology.
METHODS: In this cross-sectional study, we included 10-19-year-olds in Ukraine\u27s national TB registry who started TB treatment between 2015 and 2018. Using multivariable regression, we estimated associations between patient characteristics and four presentations of TB: pleural, extrathoracic, cavitary and rifampicin-resistant (RR). We also described the epidemiology of adolescent TB in Ukraine.
RESULTS: Among 2491 adolescent TB cases, 88.4% were microbiologically confirmed. RR-TB was confirmed in 16.9% of new and 29.7% of recurrent cases. Of 88 HIV-infected adolescents, 59.1% were not on antiretroviral therapy at TB diagnosis. Among 10-14-year-olds, boys had more pleural disease (adjusted OR (aOR) 2.12, 95% CI: 1.08-4.37). Extrathoracic TB was associated with age 15-19 years (aOR 0.26, 95% CI: 0.18-0.37) and HIV (aOR 3.25, 95% CI: 1.55-6.61 in 10-14-year-olds; aOR 8.18, 95% CI: 3.58-17.31 in 15-19-year-olds). Cavitary TB was more common in migrants (aOR 3.53, 95% CI: 1.66-7.61) and 15-19-year-olds (aOR 4.10, 95% CI: 3.00-5.73); among 15-19-year-olds, it was inversely associated with HIV (aOR 0.32, 95% CI: 0.13-0.70). RR-TB was associated with recurrent disease (aOR 1.87, 95% CI: 1.08-3.13), urban residence (aOR 1.27, 95% CI: 1.01-1.62) and cavitation (aOR 2.98, 95% CI: 2.35-3.78).
CONCLUSIONS: Age, sex, HIV and social factors impact the presentation of adolescent TB. Preventive, diagnostic and treatment activities should take these factors into consideration
Global asthma prevalence in adults: findings from the cross-sectional world health survey
<p>Abstract</p> <p>Background</p> <p>Asthma is a major cause of disability, health resource utilization and poor quality of life world-wide. We set out to generate estimates of the global burden of asthma in adults, which may inform the development of strategies to address this common disease.</p> <p>Methods</p> <p>The World Health Survey (WHS) was developed and implemented by the World Health Organization in 2002-2003. A total of 178,215 individuals from 70 countries aged 18 to 45 years responded to questions related to asthma and related symptoms. The prevalence of asthma was based on responses to questions relating to self-reported doctor diagnosed asthma, clinical/treated asthma, and wheezing in the last 12 months.</p> <p>Results</p> <p>The global prevalence rates of doctor diagnosed asthma, clinical/treated asthma and wheezing in adults were 4.3%, 4.5%, and 8.6% respectively, and varied by as much as 21-fold amongst the 70 countries. Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing (21.0%, 21.5%, and 27.4%). Amongst those with clinical/treated asthma, almost 24% were current smokers, half reported wheezing, and 20% had never been treated for asthma.</p> <p>Conclusions</p> <p>This study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide. The high prevalence of smoking remains a major barrier to combating the global burden of asthma. While the highest prevalence rates were observed in resource-rich countries, resource-poor nations were also significantly affected, posing a barrier to development as it stretches further the demands of non-communicable diseases.</p
Adolescent tuberculosis.
Adolescence is characterised by a substantial increase in the incidence of tuberculosis, a known fact since the early 20th century. Most of the world's adolescents live in low-income and middle-income countries where tuberculosis remains common, and where they comprise a quarter of the population. Despite this, adolescents have not yet been addressed as a distinct population in tuberculosis policy or within tuberculosis treatment services, and emerging evidence suggests that current models of care do not meet their needs. This Review discusses up-to-date information about tuberculosis in adolescence, with a focus on the management of infection and disease, including HIV co-infection and rifampicin-resistant tuberculosis. We outline the progress in vaccine development and highlight important directions for future research
A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naive C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)gamma-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNgamma-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNgamma+ cells, increased the expression of IFNgamma mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas\u27 heart disease
Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features
Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14 years, p < 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively—laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT
Mechanisms of vesicular stomatitis virus inactivation by protoporphyrin ix, zinc- protoporphyrin ix, and mesoporphyrin ix
© 2017 American Society for Microbiology. All Rights Reserved.Virus resistance to antiviral therapies is an increasing concern that makes the development of broad-spectrum antiviral drugs urgent. Targeting of the viral envelope, a component shared by a large number of viruses, emerges as a promising strategy to overcome this problem. Natural and synthetic porphyrins are good candidates for antiviral development due to their relative hydrophobicity and pro-oxidant character. In the present work, we characterized the antiviral activities of protoprophyrin IX (PPIX), Zn-protoporphyrin IX (ZnPPIX), and mesoporphyrin IX (MPIX) against vesicular stomatitis virus (VSV) and evaluated the mechanisms involved in this activity. Treatment of VSV with PPIX, ZnPPIX, and MPIX promoted dose-dependent virus inactivation, which was potentiated by porphyrin photoactivation. All three porphyrins inserted into lipid vesicles and disturbed the viral membrane organization. In addition, the porphyrins also affected viral proteins, inducing VSV glycoprotein cross-linking, which was enhanced by porphyrin photoactivation. Virus incubation with sodium azide and α-tocopherol partially protected VSV from inactivation by porphyrins, suggesting that singlet oxygen (1O2) was the main reactive oxygen species produced by photoactivation of these molecules. Furthermore, 1O2 was detected by 9,10-dimethylanthracene oxidation in photoactivated porphyrin samples, reinforcing this hypothesis. These results reveal the potential therapeutic application of PPIX, ZnPPIX, and MPIX as good models for broad antiviral drug design.Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ; Brazil; grant number E-26/201.167/2014), the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq; Brazil; grant number 306669/2013-7), the Coordenação de Aperfeiçoamento de Pessoal de NÃvel Superior (CAPES; Brazil; grant number CsF 171/2012), the Fundacao para a Ciencia e Tecnologia-Ministério da Educação e Ciência (FCT-MEC; Portugal; project HIVERA/0002/2013), and Marie SkÅ‚odowska-Curie Actions (MSCA; European Commission project INPACT 644167). C.C.-O. acknowledges a Science without Borders postdoctoral fellowship from CAPES (171/2012), and J.M.F. acknowledges an FCT-MEC Ph.D. fellowship (SFRH/BD/70423/2010)info:eu-repo/semantics/publishedVersio
Utilization of a mobile medical van for delivering pediatric care in the bateys of the Dominican Republic
Background Bateys are impoverished areas of housing for migrant Haitian sugar cane workers in the Dominican Republic (DR). In these regions, preventative health care is almost non-existent, public service accessibility is limited, and geographic isolation prevents utilization of care even by those families with resources. Consequently, the development of a viable mobile system is vital to the delivery of acute and preventative health care in this region. Aims This study evaluated an existing mobile medical system. The primary goal was to describe the population served, diseases treated, and resources utilized. A secondary goal was to determine qualitatively an optimal infrastructure for sustainable health care delivery within the bateys. Methods Information on basic demographic data, diagnosis, chronicity of disease, and medications dispensed was collected on all pediatric patients seen in conjunction with an existing mobile medical system over a 3-month period in the DR. Health statistics for the region were collected and interviews were conducted with health care workers (HCWs) and community members on existing and optimal health care infrastructure. Results Five hundred eighty-four pediatric patients were evaluated and treated. Median age was 5 years (range 2 weeks to 20 years), and 53.7% of patients seen were 5 years of age or younger. The mean number of complaints per patient was 2.8 (range 0 to 6). Thirty-six percent (373) of all diagnoses were for acute complaints, and 64% (657) were chronic medical problems. The most common pediatric illnesses diagnosed clinically were gastrointestinal parasitic infection (56.6%), skin/fungal infection (46.2%), upper respiratory tract infections (URIs) (22.8%), previously undiagnosed asthma and allergies (8.2%), and symptomatic anemia (7.2%). Thirty HCWs and community members were interviewed, and all cited the need for similar resources: a community clinic and hospital referral site, health promoters within each community, and the initiation of pediatric training for community HCWs. Conclusion A mobile medical system is a sustainable, efficient mechanism for delivering acute and preventive care in the Haitian bateys of the Dominican Republic. The majority of patients served were 8 years of age or younger with multiple presenting symptoms. A pediatric protocol for identifying the most appropriate drugs and supplies for mobile units in the DR can be created based upon diseases evaluated. Qualitative data from HCWs and community members identified the need for an integrative health care delivery infrastructure and community health promoters versed in pediatric care who can aid in education of batey members and monitor chronic and acute illnesses. We are planning follow-up visits to implement these programs
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