Real-Time PCR in the early detection of invasive fungal infection in immunodeficient infants and children

Background: Crucial to the diagnosis and effective therapy of invasive fungal infection (IFI) in the immunodeficient is the early identification of the causative agent especially in patients who lack clinical evidence of the disease. The standard methods for the detection of fungi in clinical specimens are direct microscopy and mycological culture. Microscopy often lacks a satisfactory sensitivity, whereas diagnosis by mycological culture often requires a long growth period. Studies have demonstrated the feasibility of detecting molds and yeast in a single reaction using the universal fungal primer. Objective: Evaluation of the role of real-time PCR in the early detection of fungal infection in immunodeficient patients with suspected IFI, who lack clinical evidence of the disease. Methods: This study included 30 immunodeficiency patients suspected of having IFI; 9 with primary and 21 with secondary immunodeficiency. All patients had at least one host factor, but no clinical criteria according to the EORTC-MSG definition of IFI. Twenty seven had fever and 3 had bronchopneumonia, both not responding to broad spectrum antibiotics for 96 hrs. or more. Blood samples were cultured for fungi and were analyzed with real-time PCR using universal fungal primers. For positive samples of fungal infection, aspergillus-specific primers were used for detection of aspergillus. Results: Seventeen patients (56.7%) proved to have IFI. Blood culture detected Candida in 2 patients only, while PCR detected Candida in another 9 and Aspergillus in 6, thus 15/17 patients with IFI (88%) were missed by blood culture. Blood culture for IFI diagnosis had a very low sensitivity (12%) but had a 100% specificity and positive predictive value. The results PCR did not vary with gender, degree of fever, immunodeficiency type, clinical presentation or current intake of antifungal treatment. Patients with proven IFI showed significantly increased CRP levels as compared to those without infection. Conclusion: Real-time PCR proved superior to culture in early diagnosis of IFI in patients with immunodeficiency before the appearance of the characteristic clinical and imaging signs. Reliance on blood culture alone at that stage would result in missing most of the positive cases with consequent delay in the initiation of specific treatment. Keywords: Invasive fungal infection, immunodeficiency, blood culture, real-time PCR, candida, aspergillusEgypt J Pediatr Allergy Immunol 2012;10(2):67-7

Analysis of the filed data of a sample of Egyptian children with bronchial asthma

Background: Identification of the clinical profile of asthma in a community is crucial to the understanding of the growing disease burden. We sought to evaluate the clinical characteristics and management outcome of a sample of asthmatic children from Cairo city and its suburbs. Methods: This retrospective study analyzed the data of 422 consecutively numbered files of asthmatic children from the Pediatric Allergy and Immunology Unit of Ain Shams University Children's Hospital. Data collected included the age at onset, duration of follow up, precipitating factors, feeding history, clinical severity, presence of other allergic diseases and outcome and course of the disease. This is besides the available results of laboratory and imaging studies and the treatment received including the routes and types of therapy. Results: The results revealed that 197 children (46.7%) had bronchial asthma only while 225 (53.3%) had concomitant allergic disorders. Males outnumbered females and urban residents outnumbered suburban and rural residents and all cases belonged to the low and middle social and economic community sectors. A positive family history of allergy in general was evident in about 40% of cases. Viral infection was the most common precipitating factor for exacerbations. Mild and moderate persistent asthma were more frequent than the severe variety (15.10%, 10.20%, and 1.50%). Serum total IgE and peripheral blood eosinophil counts were elevated and atopy was evident in most cases. Inhaled corticosteroid therapy was the most commonly prescribed treatment in the current study but compliance was generally poor. Conclusion: Wider scale multi-center studies in Cairo and other localities of Egypt are needed to outline the profile of childhood asthma in the whole country using a population rather than a referral center-based approach.Keywords: Pediatric asthma, risk factors, asthma grade, asthma triggers, smoking, residenceEgypt J Pediatr Allergy Immunol 2009;7(2):59-6

Serum neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in immature neutrophil precursors and in epithelial cells during both inflammation and neoplastic transformation. A recent prospective pediatric study demonstrated that concentrations of NGAL in urine and plasma represent novel, sensitive, and specific biomarkers for early identification of acute kidney injury following cardiac surgery. Objective: To assess the relationship of serum NGAL levels with disease activity in pediatric systemic lupus erythematosus (SLE) with special emphasis on lupus nephritis. Methods: The study included 30 children and adolescents with pediatric SLE with a mean age of 16.48±3.524 years. Patients were clinically and laboratory evaluated and categorized into those with nephritis and those without nephritis. Activity was assessed using SLEDAI score, NGAL levels were measured in the sera of included patients and were compared to those of 20 matched controls using ELISA. Results: Serum NGAL was significantly higher in SLE patients in comparison to the controls (z=-5.962, p < 0.001). Furthermore serum NGAL was significantly higher in SLE patients with nephritis and in those without nephritis in comparison to the controls (p < 0.001 in both). Serum NGAL was higher in SLE patients with nephritis in comparison to those without nephritis, yet the results are borderline regarding statistical significance (p=0.05). Levels of serum NGAL correlated significantly with disease activity as assessed by SLE disease activity index (SLEDAI) (r=0.485, p < 0.01). There was a significant correlation between serum NGAL and urinary protein to creatinine ratio, 24hr urinary protein and BUN of SLE patients. Conclusion: Our results suggest that serum NGAL represents a novel biomarker for disease activity in pediatric SLE patients, and a marker of severity of renal involvement.Keywords: SLE, NGAL, SLEDAI, lupus nephritisEgypt J Pediatr Allergy Immunol 2011;9(1):15-2

Observation of Reduced Thermal Conductivity in a Metal-Organic Framework Due to the Presence of Adsorbates

Whether the presence of adsorbates increases or decreases thermal conductivity in metal-organic frameworks (MOFs) has been an open question. Here we report observations of thermal transport in the metal-organic framework HKUST-1 in the presence of various liquid adsorbates: water, methanol, and ethanol. Experimental thermoreflectance measurements were performed on single crystals and thin films, and theoretical predictions were made using molecular dynamics simulations. We find that the thermal conductivity of HKUST-1 decreases by 40 – 80% depending on the adsorbate, a result that cannot be explained by effective medium approximations. Our findings demonstrate that adsorbates introduce additional phonon scattering in HKUST-1, which particularly shortens the lifetimes of low-frequency phonon modes. As a result, the system thermal conductivity is lowered to a greater extent than the increase expected by the creation of additional heat transfer channels. Finally, we show that thermal diffusivity is even more greatly reduced than thermal conductivity by adsorption

Hybridization from Guest-Host Interactions Reduces the Thermal Conductivity of Metal-Organic Frameworks

We experimentally and theoretically investigate the thermal conductivity and mechanical properties of polycrystalline HKUST-1 metal–organic frameworks (MOFs) infiltrated with three guest molecules: tetracyanoquinodimethane (TCNQ), 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ), and (cyclohexane-1,4-diylidene)dimalononitrile (H4-TCNQ). This allows for modification of the interaction strength between the guest and host, presenting an opportunity to study the fundamental atomic scale mechanisms of how guest molecules impact the thermal conductivity of large unit cell porous crystals. The thermal conductivities of the guest@MOF systems decrease significantly, by on average a factor of 4, for all infiltrated samples as compared to the uninfiltrated, pristine HKUST-1. This reduction in thermal conductivity goes in tandem with an increase in density of 38% and corresponding increase in heat capacity of ∼48%, defying conventional effective medium scaling of thermal properties of porous materials. We explore the origin of this reduction by experimentally investigating the guest molecules’ effects on the mechanical properties of the MOF and performing atomistic simulations to elucidate the roles of the mass and bonding environments on thermal conductivity. The reduction in thermal conductivity can be ascribed to an increase in vibrational scattering introduced by extrinsic guest-MOF collisions as well as guest molecule-induced modifications to the intrinsic vibrational structure of the MOF in the form of hybridization of low frequency modes that is concomitant with an enhanced population of localized modes. The concentration of localized modes and resulting reduction in thermal conductivity do not seem to be significantly affected by the mass or bonding strength of the guest species

Optimization procedure for intelligent Internet of Things applications

Internet of Things (IoT) is basically the concept and terminology of vehicular communications for Vehicles are becoming increasingly available in the literature. Applications for these are efficient traffic management, driving safety, and information services, which offer new service functionalities to extend efficiency for the network. In IoV, the vehicles carry advanced components such as actuators, sensors, and controllers to provide vehicle control functions and intelligent decision-making. The connectivity among vehicles is through intercommunication between devices, intelligent systems in the environment, and sensors [3]. There are three elements for a network model of IoV: client, connection, and cloud. The optimization technique finds the optimal result for sophisticated challenges by diminishing or exploiting objective functions that stand on one or more decision parameters that achieve the objective function value. This paper proposes a GA-based energy optimization procedure and assesses the performance over existing optimization techniques for intelligent IoT applications

Rhinitis associated with asthma is distinct from rhinitis alone: TARIA‐MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis.info:eu-repo/semantics/publishedVersio

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity