Hydrocephalus is a debilitating disorder, affecting all age groups. Evaluation of its global epidemiology is required for healthcare planning and resource allocation.
To define age-specific global ...prevalence and incidence of hydrocephalus.
Population-based studies reporting prevalence of hydrocephalus were identified (MEDLINE, EMBASE, Cochrane, and Google Scholar (1985-2017)). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two authors reviewed abstracts, full text articles and abstracted data. Metanalysis and meta-regressions were used to assess associations between key variables. Heterogeneity and publication bias were assessed. Main outcome of interest was hydrocephalus prevalence among pediatric (≤ 18 years), adults (19-64 years), and elderly (≥ 65) patients. Annual hydrocephalus incidence stratified by country income level and folate fortification requirements were obtained (2003-2014) from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR).
Of 2,460 abstracts, 52 met review eligibility criteria (aggregate population 171,558,651). Mean hydrocephalus prevalence was 85/100,000 95% CI 62, 116. The prevalence was 88/100,000 95% CI 72, 107 in pediatrics; 11/100,000 95% CI 5, 25 in adults; and 175/100,000 95% CI 67, 458 in the elderly. The ICBDSR-based incidence of hydrocephalus diagnosed at birth remained stable over 11 years: 81/100,000 95% CI 69, 96. A significantly lower incidence was identified in high-income countries.
This systematic review established age-specific global hydrocephalus prevalence. While high-income countries had a lower hydrocephalus incidence according to the ICBDSR registry, folate fortification status was not associated with incidence. Our findings may inform future healthcare resource allocation and study.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Role of Low Energy Expenditure and Sitting in Obesity, Metabolic Syndrome, Type 2 Diabetes, and Cardiovascular Disease
Marc T. Hamilton 1 , 2 ,
Deborah G. Hamilton 1 and
Theodore W. Zderic 1
1 ...Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri
2 Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri
Address correspondence and reprint requests to Dr. Marc T. Hamilton, E102 VMB 1600 E. Rollins Rd., Department of Biomedical
Sciences, University of Missouri-Columbia, Columbia, MO 65211. E-mail: hamiltonm{at}missouri.edu
Abstract
It is not uncommon for people to spend one-half of their waking day sitting, with relatively idle muscles. The other half
of the day includes the often large volume of nonexercise physical activity. Given the increasing pace of technological change
in domestic, community, and workplace environments, modern humans may still not have reached the historical pinnacle of physical
inactivity, even in cohorts where people already do not perform exercise. Our purpose here is to examine the role of sedentary
behaviors, especially sitting, on mortality, cardiovascular disease, type 2 diabetes, metabolic syndrome risk factors, and
obesity. Recent observational epidemiological studies strongly suggest that daily sitting time or low nonexercise activity
levels may have a significant direct relationship with each of these medical concerns. There is now a need for studies to
differentiate between the potentially unique molecular, physiologic, and clinical effects of too much sitting (inactivity
physiology) separate from the responses caused by structured exercise (exercise physiology). In theory, this may be in part
because nonexercise activity thermogenesis is generally a much greater component of total energy expenditure than exercise
or because any type of brief, yet frequent, muscular contraction throughout the day may be necessary to short-circuit unhealthy
molecular signals causing metabolic diseases. One of the first series of controlled laboratory studies providing translational
evidence for a molecular reason to maintain high levels of daily low-intensity and intermittent activity came from examinations
of the cellular regulation of skeletal muscle lipoprotein lipase (LPL) (a protein important for controlling plasma triglyceride
catabolism, HDL cholesterol, and other metabolic risk factors). Experimentally reducing normal spontaneous standing and ambulatory
time had a much greater effect on LPL regulation than adding vigorous exercise training on top of the normal level of nonexercise
activity. Those studies also found that inactivity initiated unique cellular processes that were qualitatively different from
the exercise responses. In summary, there is an emergence of inactivity physiology studies. These are beginning to raise a
new concern with potentially major clinical and public health significance: the average nonexercising person may become even
more metabolically unfit in the coming years if they sit too much, thereby limiting the normally high volume of intermittent
nonexercise physical activity in everyday life. Thus, if the inactivity physiology paradigm is proven to be true, the dire
concern for the future may rest with growing numbers of people unaware of the potential insidious dangers of sitting too much
and who are not taking advantage of the benefits of maintaining nonexercise activity throughout much of the day.
CVD, cardiovascular disease
DVT, deep venous thrombosis
FTW, fast-twitch white
LPL, lipoprotein lipase
NEAT, nonexercise activity thermogenesis
PAL, physical activity level
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 7 September 2007. DOI: 10.2337/db07-0882.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received June 28, 2007.
Accepted August 30, 2007.
DIABETES
Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models of thrombi formation in human lung microvessels that could also assess therapeutics ...and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus‐on‐a‐chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ‐level contributions to inflammation‐induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet‐endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor‐1 (PAR‐1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.
Clinical laboratory analyses aid in the diagnosis and management of human allergic (IgE-dependent) diseases. Diagnosis of immediate-type hypersensitivity begins with a thorough clinical history and ...physical examination. Once symptoms compatible with an allergic disorder have been identified, a skin test, blood test, or both for allergen-specific IgE antibodies provide confirmation of sensitization, which strengthens the diagnosis. Skin testing provides a biologically relevant immediate-type hypersensitivity response with resultant wheal-and-flare reactions within 15 minutes of allergen application. Allergen-specific IgE antibody in serum is quantified by using 3 laboratory-based autoanalyzers (ImmunoCAP, Immulite, and HYTEC-288) and novel microarray and lateral-flow immunoassays. Technologic advances in serologic allergen-specific IgE measurements have involved increased automation, with enhanced reproducibility, greater quantification, lower analytic sensitivity, and component-supplemented extract-based allergen use. In vivo provocation tests involving inhalation, ingestion, or injection of allergens serve to clarify discordant history and skin- or blood-based measures of sensitization. Other diagnostic allergy laboratory analyses include total and free serum IgE measurement, precipitating IgG antibodies specific for organic dusts, mast cell tryptase, and indicator allergen analyses to assess indoor environments to promote patient-targeted allergen avoidance programs. A critique is provided on the predictive utility of serologic measures of specific IgE for food allergy and asthma. Reasons for the lack of clinical utility for food-specific IgG/IgG4 measurements in allergy diagnosis are examined. When the specific IgE measures are inconsistent with the clinical history, they should be confirmed by means of repeat and alternative method analysis. Ultimately, the patient's clinical history remains the principal arbiter that determines the final diagnosis of allergic disease.
The neurodiversity paradigm challenges pathologising accounts of neurodevelopmental differences, including autism, attention deficit disorder (ADHD), dyslexia, developmental language disorder (DLD) ...and others. From a neurodiversity perspective, these differences in the way people perceive, learn about and interact with the world are conceptualised as naturally occurring cognitive variation, akin to biodiversity in the natural environment, which may bring unique strengths and challenges for individuals. An implication of this approach is that interventions designed to create contexts in which neurodivergent people can thrive are needed, in addition to those that seek to ameliorate individual-level difficulties. In this conceptual review, we consider how higher education can offer a context in which cognitive diversity can be noticed, welcomed and accepted with warmth. In universities, neurodiversity is one dimension of difference within an increasingly diverse student population, which overlaps - but is not synonymous - with disability. We argue that improving experience and outcomes for neurodivergent students should be a priority for universities aiming to produce graduates equipped to tackle the complex problems of contemporary society. Drawing on the foundational principles of compassion-focused psychological therapies, we consider how compassion can be enacted within interpersonal interaction, curriculum design, and leadership culture in universities. We apply the insights of double empathy theory to the problem of overcoming barriers of difference in the classroom. Finally, we make recommendations for Universal Design for Learning (UDL) and strengths-based pedagogical approaches, which create a fit-for-purpose educational environment for the widest possible range of learners. This realignment with the neurodiversity paradigm offers an antidote to bolt-on provisions for students who differ from the neuro-normative, and might enable neurodivergent thinkers to flourish within and beyond higher education.
Methane is an important greenhouse gas and its atmospheric concentration has almost tripled since pre-industrial times. It plays a central role in atmospheric oxidation chemistry and affects ...stratospheric ozone and water vapour levels. Most of the methane from natural sources in Earth's atmosphere is thought to originate from biological processes in anoxic environments. Here we demonstrate using stable carbon isotopes that methane is readily formed in situ in terrestrial plants under oxic conditions by a hitherto unrecognized process. Significant methane emissions from both intact plants and detached leaves were observed during incubation experiments in the laboratory and in the field. If our measurements are typical for short-lived biomass and scaled on a global basis, we estimate a methane source strength of 62–236 Tg yr-1 for living plants and 1–7 Tg yr-1 for plant litter (1 Tg = 1012 g). We suggest that this newly identified source may have important implications for the global methane budget and may call for a reconsideration of the role of natural methane sources in past climate change.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Although promising results have emerged regarding oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for the treatment of peanut allergy (PA), direct comparisons of these ...approaches are limited. Objective This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut OIT and SLIT. Methods In this double-blind study children with PA were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7 mg/d (SLIT) or 2000 mg/d (OIT), and subjects were rechallenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged. Results Twenty-one subjects aged 7 to 13 years were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a greater than 10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141- vs 22-fold, P = .01). Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found, with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT ( P < .001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion. Conclusion OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects.
The promise of therapeutic nucleic acids has long been tempered by difficulty in overcoming biological barriers to their delivery. The past two decades have seen the development of ionizable lipid ...nanoparticles as a vehicle for nucleic acid delivery and their translation to the clinic.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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